8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, and 67084 alt, human proteins and methods of use thereof

ABSTRACT

The invention provides isolated nucleic acids molecules, designated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules, which encode novel transporter family molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene has been introduced or disrupted. The invention still further provides isolated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, fusion polypeptides, antigenic peptides and anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies. Diagnostic methods utilizing compositions of the invention are also provided.

RELATED APPLICATIONS

[0001] This application claims the benefit of prior-filed provisional patent application Serial No. 60/256,240, filed Dec. 15, 2000, entitled “8099 AND 46455, NOVEL HUMAN SUGAR TRANSPORTERS AND USES THEREFOR,” prior-filed provisional patent application Serial No. 60/256,588, filed Dec. 18, 2000, entitled “54414 AND 53763, NOVEL HUMAN POTASSIUM CHANNELS AND USES THEREFOR,” and prior-filed provisional patent application Serial No. 60/258,028, filed Dec. 21, 2000, entitled “67076, 67102, 44181, 67084FL, and 67084alt, NOVEL HUMAN PHOSPHOLIPID TRANSPORTERS AND USES THEREOF.” The entire contents of the above-referenced applications are incorporated herein by this reference.

BACKGROUND OF THE INVENTION

[0002] Cellular membranes serve to differentiate the contents of a cell from the surrounding environment, and may also serve as effective barriers against the unregulated influx of hazardous or unwanted compounds, and the unregulated efflux of desirable compounds. Membranes are by nature impervious to the unfacilitated diffusion of hydrophilic compounds such as proteins, water molecules, and ions due to their structure: a bilayer of lipid molecules in which the polar head groups face outward (towards the exterior and interior of the cell) and the nonpolar tails face inward (at the center of bilayer, forming a hydrophobic core). Membranes enable a cell to maintain a relatively higher intracellular concentration of desired compounds and a relatively lower intracellular concentration of undesired compounds than are contained within the surrounding environment.

[0003] Membranes also present a structural difficulty for cells, in that most desired compounds cannot readily enter the cell, nor can most waste products readily exit the cell through this lipid bilayer. The import and export of such compounds is regulated by proteins which are embedded (singly or in complexes) in the cellular membrane. Two mechanisms exists whereby membrane proteins allow the passage of compounds: non-mediated and mediated transport. Simple diffusion is an example of non-mediated transport, while facilitated diffusion and active transport are examples of mediated transport. Permeases, porters, translocases, translocators, and transporters are proteins that engage in mediated transport (Voet and Voet (1990) Biochemistry, John Wiley and Sons, Inc., New York, N.Y. pp. 484-505).

[0004] Sugar transporters are members of the major facilitator superfamily of transporters. These transporters are passive in the sense that they are driven by the substrate concentration gradient and they exhibit distinct kinetics as well as sugar substrate specificity. Members of this family share several characteristics: (1) they contain twelve transmembrane domains separated by hydrophilic loops; (2) they have intracellular N- and C-termini; and (3) they are thought to function as oscillating pores. The transport mechanism occurs via sugar binding to the exofacial binding site of the transporter, which is thought to trigger a conformational change causing the sugar binding site to re-orient to the endofacial conformation, allowing the release of substrate. These transporters are specific for various sugars and are found in both prokaryotes and eukaryotes. In mammals, sugar transporters transport various monosaccharides across the cell membrane (Walmsley et al. (1998) Trends in Biochem. Sci. 23:476-481; Barrett et al (1999) Curr. Op. Cell Biol. 11:496-502).

[0005] At least nine mammalian glucose transporters have been identified, GLUT1-GLUT9, which are expressed in a tissue-specific manner (e.g., in brain, erythrocyte, kidney, muscle, and adipose tissues) (Shepherd et al. (1999) N. Engl. J. Med. 341:248-257; Doege et al. (2000) Biochem. J. 350:771-776). Some GLUT proteins have been shown to be present in low amounts at the plasma membrane during the basal state, at which time large amounts are sequestered in intracellular vesicle stores. Stimulatory molecules specific for each GLUT (such as insulin) regulate the translocation of the GLUT-containing vesicles to the plasma membrane. The vesicles fuse at the membrane and subsequently expose the GLUT protein to the extracellular milieu to allow glucose (and other monosaccharide) transport into the cell (Walmsley et al. (1998) Trends in Biochem. Sci. 23:476-481; Barrett et al. (1999) Curr. Op. Cell Biol. 11:496-502). Other GLUT transporters play a role in constitutive sugar transport.

[0006] Potassium (K⁺) channels are ubiquitous proteins which are involved in the setting of the resting membrane potential as well as in the modulation of the electrical activity of cells. In excitable cells, K⁺ channels influence action potential waveforms, firing frequency, and neurotransmitter secretion (Rudy, B. (1988) Neuroscience, 25, 729-749; Hille, B. (1992) Ionic Channels of Excitable Membranes, 2nd Ed.). In non-excitable cells, they are involved in hormone secretion, cell volume regulation and potentially in cell proliferation and differentiation (Lewis et al. (1995) Annu. Rev. Immunol., 13, 623-653). Developments in electrophysiology have allowed the identification and the characterization of an astonishing variety of K⁺ channels that differ in their biophysical properties, pharmacology, regulation and tissue distribution (Rudy, B. (1988) Neuroscience, 25, 729-749; Hille, B. (1992) Ionic Channels of Excitable Membranes, 2nd Ed.). More recently, cloning efforts have shed considerable light on the mechanisms that determine this functional diversity. Furthermore, analyses of structure-function relationships have provided an important set of data concerning the molecular basis of the biophysical properties (selectivity, gating, assembly) and the pharmacological properties of cloned K⁺ channels.

[0007] Functional diversity of K⁺ channels arises mainly from the existence of a great number of genes coding for pore-forming subunits, as well as for other associated regulatory subunits. Two main structural families of pore-forming subunits have been identified. The first one consists of subunits with a conserved hydrophobic core containing six transmembrane domains (T_(M)Ds). These K⁺ channel α subunits participate in the formation of outward rectifier voltage-gated (Kv) and Ca²⁺-dependent K⁺ channels. The fourth T_(M)D contains repeated positive charges involved in the voltage gating of these channels and hence in their outward rectification (Logothetis et al. (1992) Neuron, 8, 531-540; Bezanilla et al. (1994) Biophys. J. 66, 1011-1021).

[0008] The second family of pore-forming subunits have only two T_(M)Ds. They are essential subunits of inward-rectifying (IRK), G-protein-coupled (GIRK) and ATP-sensitive (K_(ATP)) K⁺ channels. The inward rectification results from a voltage-dependent block by cytoplasmic Mg²⁺ and polyamines (Matsuda, H. (1991) Annu. Rev. Physiol., 53, 289-298). A conserved domain, called the P domain, is present in all members of both families (Pongs, O. (1993) J. Membr. Biol., 136, 1-8; Heginbotham et al. (1994) Biophys. J. 66,1061-1067; Mackinnon, R. (1995) Neuron, 14, 889-892; Pascual et al., (1995) Neuron., and 14, 1055-1063). This domain is an essential element of the aqueous K⁺-selective pore. In both groups, the assembly of four subunits is necessary to form a functional K⁺ channel (Mackinnon, R. (1991) Nature, 350, 232-235; Yang et al., (1995) Neuron, 15, 1441-1447.

[0009] In both six T_(M)D and two T_(M)D pore-forming subunit families, different subunits coded by different genes can associate to form heterotetramers with new channel properties (Isacoff et al., (1990) Nature, 345, 530-534). A selective formation of heteropolymeric channels may allow each cell to develop the best K⁺ current repertoire suited to its function. Pore-forming α subunits of Kv channels are classified into different subfamilies according to their sequence similarity (Chandy et al. (1993) Trends Pharmacol. Sci., 14: 434). Tetramerization is believed to occur preferentially between members of each subgroup (Covarrubias et al. (1991) Neuron, 7, 763-773). The domain responsible for this selective association is localized in the N-terminal region and is conserved between members of the same subgroup. This domain is necessary for hetero- but not homo-multimeric assembly within a subfamily and prevents co-assembly between subfamilies. Recently, pore-forming subunits with two T_(M)Ds were also shown to co-assemble to form heteropolymers (Duprat et al. (1995) Biochem. Biophys. Res. Commun., 212, 657-663. This heteropolymerization seems necessary to give functional GIRKs. IRKs are active as homopolymers but also form heteropolymers.

[0010] New structural types of K⁺ channels were identified recently in both humans and yeast. These channels have two P domains in their functional subunit instead of only one (Ketchum et al. (1995) Nature, 376, 690-695; Lesage et al. (1996) J. Biol. Chem., 271, 4183-4187; Lesage et al. (1996) EMBO J., 15, 1004-1011; Reid et al. (1996) Receptors Channels 4, 51-62). The human channel called TWIK- 1, has four T_(M)Ds. TWIK- 1 is expressed widely in human tissues and is particularly abundant in the heart and the brain. TWIK-1 currents are time independent and inwardly rectifying. These properties suggest that TWIK-1 channels are involved in the control of the background K⁺ membrane conductance (Lesage et al. (1996) EMBO J., 15, 1004-1011).

[0011] Potassium channels are potassium ion selective, and can determine membrane excitability (the ability of, for example, a neuron to respond to a stimulus and convert it into an impulse). Potassium channels can also influence the resting potential of membranes, wave forms and frequencies of action potentials, and thresholds of excitation. Potassium channels are typically expressed in electrically excitable cells, e.g., neurons, muscle, endocrine, and egg cells, and may form heteromultimeric structures, e.g., composed of pore-forming and cytoplasmic subunits. Potassium channels may also be found in non-excitable cells, where they may play a role in, e.g., signal transduction. Examples of potassium channels include: (1) the voltage-gated potassium channels, (2) the ligand-gated potassium channels, e.g., neurotransmitter-gated potassium channels, and (3) cyclic-nucleotide-gated potassium channels. Voltage-gated and ligand-gated potassium channels are expressed in the brain, e.g., in brainstem monoaminergic and forebrain cholinergic neurons, where they are involved in the release of neurotransmitters, or in the dendrites of hippocampal and neocortical pyramidal cells, where they are involved in the processes of learning and memory formation. For a detailed description of potassium channels, see Kandel E. R. et al., Principles of Neural Science, second edition, (Elsevier Science Publishing Co., Inc., N.Y. (1985)), the contents of which are incorporated herein by reference.

[0012] The E1-E2 ATPase family is a large superfamily of transport enzymes that contains at least 80 members found in diverse organisms such as bacteria, archaea, and eukaryotes (Palmgren, M. G. and Axelsen, K. B. (1998) Biochim. Biophys. Acta. 1365:37-45). These enzymes are involved in ATP hydrolysis-dependent transmembrane movement of a variety of inorganic cations (e.g., H⁺, Na⁺, K⁺, Ca²⁺, Cu²⁺, Cd⁺, and Mg²⁺ ions) across a concentration gradient, whereby the enzyme converts the free energy of ATP hydrolysis into electrochemical ion gradients. E1-E2 ATPases are also known as “P-type” ATPases, referring to the existence of a covalent high-energy phosphoryl-enzyme intermediate in the chemical reaction pathway of these transporters. Until recently, the superfamily contained four major groups: Ca²⁺ transporting ATPases; Na⁺/K⁺- and gastric H⁺/K⁺ transporting ATPases; plasma membrane H⁺ transporting ATPases of plants, fungi, and lower eukaryotes; and all bacterial P-type ATPases (Kuhlbrandt et al. (1998) Curr. Opin. Struct. Biol. 8:510-516).

[0013] E1-E2 ATPases are phosphorylated at a highly conserved DKTG sequence. Phosphorylation at this site is thought to control the enzyme's substrate affinity. Most E1-E2 ATPases contain ten alpha-helical transmembrane domains, although additional domains may be present. A majority of known gated-pore translocators contain twelve alpha-helices, including Na²⁺/H²⁺ antiporters (West (1997) Biochim. Biophys. Acta 1331:213-234).

[0014] Members of the E1-E2 ATPase superfamily are able to generate electrochemical ion gradients which enable a variety of processes in the cell such as absorption, secretion, transmembrane signaling, nerve impulse transmission, excitation/contraction coupling, and growth and differentiation (Scarborough (1999) Curr. Op. Cell Biol. 11:517-522). These molecules are thus critical to normal cell function and well-being of the organism.

[0015] Recently, a new class of E1-E2 ATPases was identified, the aminophospholipid transporters or translocators. These transporters transport not cations, but phospholipids (Tang, X. et al. (1996) Science 272:1495-1497; Bull, L. N. et al. (1998) Nat. Genet. 18:219-224; Mauro, I. et al. (1999) Biochem. Biophys. Res. Commun. 257:333-339). These transporters are involved in cellular functions including bile acid secretion and maintenance of the asymmetrical integrity of the plasma membrane.

[0016] Given the important biological and physiological roles played by the sugar transporter family of proteins, the potassium channel family of proteins, and the E1-E2 ATPase family of proteins, there exists a need to identify novel potassium channel family members for use in a variety of diagnostic/prognostic, as well as therapeutic applications

SUMMARY OF THE INVENTION

[0017] The present invention is based, at least in part, on the discovery of novel human sugar transporter family members, referred to herein as “8099 and 46455” nucleic acid and polypeptide molecules. The 8099 and 46455 nucleic acid and polypeptide molecules of the present invention are useful as modulating agents in regulating a variety of cellular processes, e.g., sugar homeostasis. Accordingly, in one aspect, this invention provides isolated nucleic acid molecules encoding 8099 and 46455 polypeptides or biologically active portions thereof, as well as nucleic acid fragments suitable as primers or hybridization probes for the detection of 8099 and 46455-encoding nucleic acids.

[0018] The present invention is also based, at least in part, on the discovery of novel potassium channel family members, referred to herein as “54414 and 53763” nucleic acid and polypeptide molecules. The 54414 and 53763 nucleic acid and protein molecules of the present invention are useful as modulating agents in regulating a variety of cellular processes, e.g., gene expression, intra- or intercellular signaling, and/or membrane excitability or conductance. Accordingly, in one aspect, this invention provides isolated nucleic acid molecules encoding 54414 and 53763 proteins or biologically active portions thereof, as well as nucleic acid fragments suitable as primers or hybridization probes for the detection of 54414 and 53763-encoding nucleic acids.

[0019] The present invention is also based, at least in part, on the discovery of novel human phospholipid transporter family members, referred to herein as “67076, 67102, 44181, 67084FL, or 67084alt” nucleic acid and polypeptide molecules. The 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid and polypeptide molecules of the present invention are useful as modulating agents in regulating a variety of cellular processes, e.g., phospholipid transport (e.g., aminophospholipid transport), absorption, secretion, gene expression, intra- or inter-cellular signaling, and/or cellular proliferation, growth, apoptosis, and/or differentiation. Accordingly, in one aspect, this invention provides isolated nucleic acid molecules encoding 67076, 67102, 44181, 67084FL, or 67084alt polypeptides or biologically active portions thereof, as well as nucleic acid fragments suitable as primers or hybridization probes for the detection of 67076, 67102, 44181, 67084FL, or 67084alt-encoding nucleic acids.

[0020] In one embodiment, the invention features an isolated nucleic acid molecule that includes the nucleotide sequence set forth in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:27. In another embodiment, the invention features an isolated nucleic acid molecule that encodes a polypeptide including the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26. In another embodiment, the invention features an isolated nucleic acid molecule that includes the nucleotide sequence contained in the plasmid deposited with ATCC® as Accession Number ______, ______, _____, _____, or ______.

[0021] In still other embodiments, the invention features isolated nucleic acid molecules including nucleotide sequences that are substantially identical (e.g., 60% identical) to the nucleotide sequence set forth as SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:27. The invention further features isolated nucleic acid molecules including at least 50 contiguous nucleotides of the nucleotide sequence set forth as SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:27. In another embodiment, the invention features isolated nucleic acid molecules which encode a polypeptide including an amino acid sequence that is substantially identical (e.g., 60% identical) to the amino acid sequence set forth as SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26. The present invention also features nucleic acid molecules which encode allelic variants of the polypeptide having the amino acid sequence set forth as SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26. In addition to isolated nucleic acid molecules encoding full-length polypeptides, the present invention also features nucleic acid molecules which encode fragments, for example, biologically active or antigenic fragments, of the full-length polypeptides of the present invention (e.g., fragments including at least 10 contiguous amino acid residues of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26). In still other embodiments, the invention features nucleic acid molecules that are complementary to, antisense to, or hybridize under stringent conditions to the isolated nucleic acid molecules described herein.

[0022] In another aspect, the invention provides vectors including the isolated nucleic acid molecules described herein (e.g., 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-encoding nucleic acid molecules). Such vectors can optionally include nucleotide sequences encoding heterologous polypeptides. Also featured are host cells including such vectors (e.g., host cells including vectors suitable for producing 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules and polypeptides).

[0023] In another aspect, the invention features isolated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides and/or biologically active or antigenic fragments thereof. Exemplary embodiments feature a polypeptide including the amino acid sequence set forth as SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, a polypeptide including an amino acid sequence at least 60% identical to the amino acid sequence set forth as SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, a polypeptide encoded by a nucleic acid molecule including a nucleotide sequence at least 60% identical to the nucleotide sequence set forth as SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:27. Also featured are fragments of the full-length polypeptides described herein (e.g., fragments including at least 10 contiguous amino acid residues of the sequence set forth as SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26) as well as allelic variants of the polypeptide having the amino acid sequence set forth as SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26.

[0024] The 8099 and 46455 polypeptides and/or biologically active or antigenic fragments thereof, are useful, for example, as reagents or targets in assays applicable to treatment and/or diagnosis of 8099 and 46455 mediated or related disorders. In one embodiment, 8099 and/or 46455 polypeptides or fragments thereof, have an 8099 and/or 46455 activity. In another embodiment, 8099 and/or 46455 polypeptides or fragments thereof, have at least one, preferably two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve transmembrane domains and/or a sugar transporter family domain, and optionally, have an 8099 and/or 46455 activity.

[0025] The 54414 and 53763 polypeptides and/or biologically active or antigenic fragments thereof, are useful, for example, as reagents or targets in assays applicable to treatment and/or diagnosis of 54414 and 53763 mediated or related disorders. In one embodiment, a 54414 AND 53763 polypeptide or fragment thereof has a 54414 and 53763 activity. In another embodiment, a 54414 and 53763 polypeptide or fragment thereof has at least one or more of the following domains or motifs: a transmembrane domain, an ion transport protein domain, a K⁺ channel tetramerisation domain, a P-loop motif, a pore domain, a potassium channel signature sequence motif, and/or a voltage sensor motif, and optionally, has a 54414 or 53763 activity.

[0026] The 67076, 67102, 44181, 67084FL, or 67084alt polypeptides and/or biologically active or antigenic fragments thereof, are useful, for example, as reagents or targets in assays applicable to treatment and/or diagnosis of 67076, 67102, 44181, 67084FL, or 67084alt associated or related disorders. In one embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or fragment thereof, has a 67076, 67102, 44181, 67084FL, or 67084alt activity. In another embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or fragment thereof, includes at least one of the following domains, sites, or motifs: a transmembrane domain, an N-terminal large extramembrane domain, a C-terminal large extramembrane domain, an E1-E2 ATPases phosphorylation site, a P-type ATPase sequence 1 motif, a P-type ATPase sequence 2 motif, a P-type ATPase sequence 3 motif, and/or one or more phospholipid transporter specific amino acid resides, and optionally, has a 67076, 67102, 44181, 67084FL, or 67084alt activity.

[0027] In a related aspect, the invention features antibodies (e.g., antibodies which specifically bind to any one of the polypeptides described herein) as well as fusion polypeptides including all or a fragment of a polypeptide described herein.

[0028] The present invention further features methods for detecting 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides and/or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules, such methods featuring, for example, a probe, primer or antibody described herein. Also featured are kits, e.g., kits for the detection of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides and/or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules. In a related aspect, the invention features methods for identifying compounds which bind to and/or modulate the activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule described herein. Further featured are methods for modulating a 67076, 67102, 44181, 67084FL, or 67084alt activity.

[0029] Other features and advantages of the invention will be apparent from the following detailed description and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] FIGS. 1A-1B depict the cDNA sequence and predicted amino acid sequence of human 8099. The nucleotide sequence corresponds to nucleic acids 1 to 2725 of SEQ ID NO:1. The amino acid sequence corresponds to amino acids 1 to 617 of SEQ ID NO:2. The coding region without the 5′ and 3′ untranslated regions of the human 8099 gene is shown in SEQ ID NO:3.

[0031]FIG. 2 depicts a structural, hydrophobicity, and antigenicity analysis of the human 8099 polypeptide (SEQ ID NO:2).

[0032] FIGS. 3A-C depicts the results of a search which was performed against the HMM database in PFAM.

[0033]FIG. 4 depicts an alignment of the human 8099 amino acid sequence (SEQ ID NO:2) with the amino acid sequence of the E. coli galactose-proton symporter GALP using the CLUSTAL W (1.74) alignment program (having GenBank Accession No. P37021, set forth as SEQ ID NO:28).

[0034]FIG. 5 depicts an alignment of the human 8099 amino acid sequence (SEQ ID NO:2) with the amino acid sequence of the E. coli arabinose-proton symporter ARAE using the CLUSTAL W (1.74) alignment program (having GenBank Accession No. P09830, set forth as SEQ ID NO:29).

[0035]FIG. 6 depicts an alignment of the human 8099 amino acid sequence (SEQ ID NO:2) with the amino acid sequence of E. coli GALP and ARAE using the CLUSTAL W (1.74) alignment program (having GenBank Accession Nos. P37021 and P09830, respectively, set forth as SEQ ID NOs:28 and 29, respectively).

[0036]FIG. 7 depicts an alignment of the human 8099 amino acid sequence (SEQ ID NO:2) with the amino acid sequence of the H. sapiens facilitative glucose transporter GLUT8 using the CLUSTAL W (1.74) alignment program (having GenBank Accession No. Y02168, set forth as SEQ ID NO:30).

[0037] FIGS. 8A-B depict the cDNA sequence and predicted amino acid sequence of human 46455. The nucleotide sequence corresponds to nucleic acids 1 to 2230 of SEQ ID NO:4. The amino acid sequence corresponds to amino acids 1 to 528 of SEQ ID NO:5. The coding region without the 5′ and 3′ untranslated regions of the human 46455 gene is shown in SEQ ID NO:6.

[0038]FIG. 9 depicts a structural, hydrophobicity, and antigenicity analysis of the human 46455 polypeptide (SEQ ID NO:5).

[0039] FIGS. 10A-C depicts the results of a search which was performed against the HMM database in PFAM.

[0040]FIG. 11 depicts an alignment of the human 46455 amino acid sequence (SEQ ID NO:5) with the amino acid sequence of C. elegans Z92825 using the CLUSTAL W (1.74) alignment program (having GenBank Accession No. Z92825, set forth as SEQ ID NO:31).

[0041] FIGS. 12A-D depicts the nucleotide sequence of the human 54414 cDNA and the corresponding amino acid sequence. The nucleotide sequence corresponds to nucleic acids 1 to 4632 of SEQ ID NO:7. The amino acid sequence corresponds to amino acids 1 to 1118 of SEQ ID NO:8. The coding region without the 5′ or 3′ untranslated regions of the human 54414 gene is shown in SEQ ID NO:9.

[0042]FIG. 13 depicts a structural, hydrophobicity, and antigenicity analysis of the human 54414 polypeptide (SEQ ID NO:8). The locations of the 6 transmembrane domains, as well as the pore domain (P), are indicated.

[0043]FIG. 14 depicts the results of a search in the HMM database, using the amino acid sequence of human 54414.

[0044] FIGS. 15A-B depicts a Clustal W (1.74) multiple sequence alignment of the human 54414 amino acid sequence (54414.prot; SEQ ID NO:8) and the amino acid sequence of the Rattus norvegicus Slack potassium channel subunit (AF089730; SEQ ID NO:32; GenBank Accession No. AAC83350). Amino acid identities are indicated by stars. The six transmembrane domains (TM1, TM2, etc.) are boxed. The pore domain, which contains the potassium channel signature sequence motif, is also boxed.

[0045] FIGS. 16A-C depicts the nucleotide sequence of the human 53763 cDNA and the corresponding amino acid sequence. The nucleotide sequence corresponds to nucleic acids 1 to 2847 of SEQ ID NO:10. The amino acid sequence corresponds to amino acids 1 to 638 of SEQ ID NO:11. The coding region without the 5′ or 3′ untranslated regions of the human 53763 gene is shown in SEQ ID NO:12.

[0046]FIG. 17 depicts a structural, hydrophobicity, and antigenicity analysis of the human 53763 polypeptide (SEQ ID NO:11). The locations of the 6 transmembrane domains, as well as the pore domain (P), are indicated.

[0047] FIGS. 18A-B depicts the results of a search in the HMM database, using the amino acid sequence of human 53763.

[0048]FIG. 19 depicts a Clustal W (1.74) sequence alignment of the human 53763 amino acid sequence (Fbh53763pat; SEQ ID NO:11) and the amino acid sequence of the Rattus norvegicus voltage-gated potassium channel protein KV3.2 (KSHIIIA) (ratCIKE; SEQ ID NO:33; GenBank Accession No. P22462). Amino acid identities are indicated by stars. The six transmembrane domains (TM1, TM2, etc.) are boxed. The pore domain, which contains the potassium channel signature sequence motif, is also boxed. Plus signs (+) at every third position of the fourth transmembrane domain (TM4), indicate the positively charged residues of the voltage sensor.

[0049] FIGS. 20A-E depicts the CDNA sequence and predicted amino acid sequence of human 67076. The nucleotide sequence corresponds to nucleic acids 1 to 6582 of SEQ ID NO:13. The amino acid sequence corresponds to amino acids 1 to 1129 of SEQ ID NO:14. The coding region without the 5′ and 3′ untranslated regions of the human 67076 gene is shown in SEQ ID NO:15.

[0050]FIG. 21 depicts a structural, hydrophobicity, and antigenicity analysis of the human 67076 polypeptide (SEQ ID NO:14).

[0051]FIG. 22 depicts the results of a search in the HMM database, using the amino acid sequence of human 67076.

[0052] FIGS. 23 depicts a Clustal W (1.74) alignment of the human 67076 amino acid sequence (“Fbh67076FL”; SEQ ID NO:14) with the amino acid sequence of mouse Potential Phospholipid-Transporting ATPase 1H (mouseAT1H) (GenBank Accession No. P98197) (SEQ ID NO:34). The transmembrane domains (“TM1”, “TM2”, etc.), E1-E2 ATPases phosphorylation site (“phosphorylation site”), and phospholipid transporter specific amino acid residues (“phospholipid transport”) are boxed.

[0053] FIGS. 24A-E depicts the cDNA sequence and predicted amino acid sequence of human 67102. The nucleotide sequence corresponds to nucleic acids 1 to 6074 of SEQ ID NO:16. The amino acid sequence corresponds to amino acids 1 to 1426 of SEQ ID NO:17. The coding region without the 5′ and 3′ untranslated regions of the human 67102 gene is shown in SEQ ID NO:18.

[0054]FIG. 25 depicts a structural, hydrophobicity, and antigenicity analysis of the human 67102 polypeptide (SEQ ID NO:17).

[0055] FIGS. 26A-B depicts the results of a search in the HMM database, using the amino acid sequence of human 67102.

[0056] FIGS. 27A-B depicts a Clustal W (1.74) alignment of the human 67102 amino acid sequence (“Fbh67102FL”; SEQ ID NO:17) with the amino acid sequence of mouse Potential Phospholipid-Transporting ATPase VA (mouseAT5A) (GenBank Accession No. 054827) (SEQ ID NO:35). The transmembrane domains (“TM1”, “TM2”, etc.), E1-E2 ATPases phosphorylation site (“phosphorylation site”), and phospholipid transporter specific amino acid residues (“phospholipid transport”) are boxed.

[0057] FIGS. 28A-E depicts the cDNA sequence and predicted amino acid sequence of human 44181. The nucleotide sequence corresponds to nucleic acids 1 to 7221 of SEQ ID NO:19. The amino acid sequence corresponds to amino acids 1 to 1177 of SEQ ID NO:20. The coding region without the 5′ and 3′ untranslated regions of the human 44181 gene is shown in SEQ ID NO:21.

[0058]FIG. 29 depicts a structural, hydrophobicity, and antigenicity analysis of the human 44181 polypeptide (SEQ ID NO:20).

[0059] FIGS. 30A-B depicts the results of a search in the HMM database, using the amino acid sequence of human 44181.

[0060] FIGS. 31A-B depicts a Clustal W (1.74) multiple sequence alignment of the human 44181 amino acid sequence (“Fbh44181”; SEQ ID NO:20) with the amino acid sequence of mouse Potential Phospholipid-Transporting ATPase IH (mouseATlH) (GenBank Accession No. P98197) (SEQ ID NO:34) and 67076 (“Fbh67076FL”; SEQ ID NO:14). The transmembrane domains (“TM1”, “TM2”, etc.), E1-E2 ATPases phosphorylation site (“phosphorylation site”), and phospholipid transporter specific amino acid residues (“phospholipid transport”) are boxed.

[0061] FIGS. 32A-D depicts the cDNA sequence and predicted amino acid sequence of human 67084FL. The nucleotide sequence corresponds to nucleic acids 1 to 4198 of SEQ ID NO:22. The amino acid sequence corresponds to amino acids 1 to 1084 of SEQ ID NO:23. The coding region without the 5′ and 3′ untranslated regions of the human 67084FL gene is shown in SEQ ID NO:24.

[0062]FIG. 33 depicts a structural, hydrophobicity, and antigenicity analysis of the human 67084FL polypeptide (SEQ ID NO:23).

[0063] FIGS. 34A-B depicts the results of a search in the HMM database, using the amino acid sequence of human 67084FL.

[0064] FIGS. 35A-B depicts a Clustal W (1.74) alignment of the human 67084FL amino acid sequence (“Fbh67084FL”; SEQ ID NO:23) with the amino acid sequence of mouse Potential Phospholipid-Transporting ATPase IIV (mouseAT2B) (GenBank Accession No.:P98195) (SEQ ID NO:36). The transmembrane domains (“TM1”, “TM2”, etc.), E1-E2 ATPases phosphorylation site (“phosphorylation site”), and phospholipid transporter specific amino acid residues (“phospholipid transport”) are boxed.

[0065] FIGS. 36A-D depicts the cDNA sequence and predicted amino acid sequence of human 67084alt. The nucleotide sequence corresponds to nucleic acids 1 to 4231 of SEQ ID NO:25. The amino acid sequence corresponds to amino acids 1 to 1095 of SEQ ID NO:26. The coding region without the 5′ and 3′ untranslated regions of the human 67084alt gene is shown in SEQ ID NO:27.

[0066]FIG. 37 depicts a structural, hydrophobicity, and antigenicity analysis of the human 67084alt polypeptide (SEQ ID NO:26).

[0067] FIGS. 38A-B depicts the results of a search in the HMM database, using the amino acid sequence of human 67084.

[0068] FIGS. 39A-B depicts a Clustal W (1.74) alignment of the human 67084alt amino acid sequence (“Fbh67084alt”; SEQ ID NO:26) with the amino acid sequence of mouse Potential Phospholipid-Transporting ATPase IIV (mouseAT2B) (GenBank Accession No.:P98195) (SEQ ID NO:36). The transmembrane domains (“TM1”, “TM2”, etc.), E1-E2 ATPases phosphorylation site (“phosphorylation site”), and phospholipid transporter specific amino acid residues (“phospholipid transport”) are boxed.

DETAILED DESCRIPTION OF THE INVENTION

[0069] The present invention is based, at least in part, on the discovery of novel sugar transporter family molecules, referred to herein as “8099 and 46455” nucleic acid and polypeptide molecules. These novel molecules are capable of, for example, modulating a transporter mediated activity (e.g., a sugar transporter mediated activity) in a cell, e.g., a liver cell, fat cell, muscle cell, or blood cell, such as an erythrocyte. These novel molecules are capable of transporting molecules, e.g., hexoses such as D-glucose, D-fructose, D-galactose or mannose across biological membranes and, thus, play a role in or function in a variety of cellular processes, e.g., maintenance of sugar homeostasis. Thus the 8099 and 46455 molecules of the present invention provide novel diagnostic targets and therapeutic agents to control 8099 and 46455-associated disorders, as defined herein.

[0070] The present invention is also based, at least in part, on the discovery of novel potassium channel family members, referred to herein as “54414 and 53763” nucleic acid and polypeptide molecules. These novel molecules are capable of, for example, modulating PCH mediated activities in a cell, e.g., a neuronal cell. Thus, the 54414 and 53763 molecules of the present invention provide novel diagnostic targets and therapeutic agents to control 54414 or 53763 -associated disorders, as defined herein.

[0071] The present invention also is based, at least in part, on the discovery of novel phospholipid transporter family molecules, referred to herein as “67076, 67102, 44181, 67084FL, or 67084alt” nucleic acid and polypeptide molecules. These novel molecules are capable of for example, transporting phospholipids (e.g., aminophospholipids such as phosphatidylserine and phosphatidylethanolamine, choline phospholipids such as phosphatidylcholine and sphingomyelin, and bile acids) across cellular membranes and, thus, play a role in or function in a variety of cellular processes, e.g., phospholipid transport, absorption, secretion, gene expression, intra- or inter-cellular signaling, and/or cellular proliferation, growth, and/or differentiation. Thus, the 67076, 67102, 44181, 67084FL, and 67084alt molecules of the present invention provide novel diagnostic targets and therapeutic agents to control 67076, 67102, 44181, 67084FL, or 67084alt-associated disorders, as defined herein.

[0072] The term “family” when referring to the protein and nucleic acid molecules of the invention is intended to mean two or more proteins or nucleic acid molecules having a common structural domain or motif and having sufficient amino acid or nucleotide sequence homology as defined herein. Such family members can be naturally or non-naturally occurring and can be from either the same or different species. For example, a family can contain a first protein of human origin as well as other distinct proteins of human origin or alternatively, can contain homologues of non-human origin, e.g., rat or mouse proteins. Members of a family can also have common functional characteristics.

[0073] 8099 and 46455 Molecules of the Invention

[0074] The family of 8099 and 46455 polypeptides comprise at least one “transmembrane domain” and at least one, preferably two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve transmembrane domains. As used herein, the term “transmembrane domain” includes an amino acid sequence of about 20-45 amino acid residues in length which spans the plasma membrane. More preferably, a transmembrane domain includes about at least 20, 25, 30, 35, 40, or 45 amino acid residues and spans the plasma membrane. Transmembrane domains are rich in hydrophobic residues, and typically have an alpha-helical structure. In a preferred embodiment, at least 50%, 60%, 70%, 80%, 90%, 95% or more of the amino acids of a transmembrane domain are hydrophobic, e.g., leucines, isoleucines, alanines, valines, phenylalanines, prolines or methionines. Transmembrane domains are described in, for example, Zagotta W. N. et al, (1996) Annual Rev. Neurosci. 19: 235-263, the contents of which are incorporated herein by reference. A MEMSAT and additional analyses resulted in the identification of twelve transmembrane domains in the amino acid sequence of human 8099 (SEQ ID NO:2) at about residues 32-49, 81-101, 109-130, 138-156, 165-184, 198-217, 279-301, 315-338, 346-364, 463-487, 499-521, and 529-549. A MEMSAT and additional analyses resulted in the identification of twelve transmembrane domains in the amino acid sequence of human 46455 (SEQ ID NO:5) at about residues 58-74,98-118, 126-145, 165-181, 188-205,218-238, 273-294,323-341,357-377, 386-410, 423-441, and 462-485.

[0075] Accordingly, 8099 and 46455 polypeptides having at least 50-60% homology, preferably about 60-70%, more preferably about 70-80%, or about 80-90% homology with at least one, preferably at least two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve transmembrane domains of human 8099 and 46455, respectively are within the scope of the invention.

[0076] Another embodiment of the invention features 8099 molecules which contain an N-terminal unique domain. The term “unique N-terminal domain” as used herein, refers to a protein domain of an 8099 protein family member which includes amino acid residues N-terminal to the sixth transmembrane domain, e.g., the GLUT8-like domain in the amino acid sequence of the 8099 protein. As used herein, a “unique N-terminal domain” refers to a protein domain which is at least about 150-200 amino acid residues in length, preferably at least about 160-190 amino acid residues in length and shares significantly more sequence homology with about residues 1 to 178 of SEQ ID NO:2 than with about residues 1 to 178 of GLUT8.

[0077] Accordingly, 8099 polypeptides having at least 50-60% homology, preferably about 60-70%, more preferably about 70-80%, or about 80-90% homology with at least one unique N-terminal domain of human 8099 (e.g., about amino acids 1-178 of SEQ ID NO:2) are within the scope of the invention.

[0078] Yet another aspect of the invention features 8099 proteins having an “extended exofacial loop” between transmembrane domains 9 and 10. Preferably, the first amino acid residue of an extended exofacial loop of 8099 is the first residue C-terminal to the amino acid residues of transmembrane domain 9 and the last residue of the exofacial loop is the first residue N-terminal to the amino acid residues of transmembrane domain 10 of 8099. In a preferred embodiment, an extended exofacial loop is at least about 50-55, 55-60, 60-65, 65-70, 70-75, 75-80, 80-85, 85-90, 90-95, 97 or more amino acid residues in length. For example, in one embodiment, an 8099 protein includes an “extended exofacial loop” of about amino acids 365-462 of SEQ ID NO:2 (97 amino acid residues in length).

[0079] Accordingly, 8099 polypeptides having at least 50-60% homology, preferably about 60-70%, more preferably about 70-80%, or about 80-90% homology with at least one extended exofacial loop of human 8099 are within the scope of the invention.

[0080] In another embodiment, an 8099 and/or 46455 molecule of the present invention is identified based on the presence of at least one “sugar transporter family domain.” As used herein, the term “sugar transporter family domain” includes a protein domain having at least about 300-600 amino acid residues and a sugar transporter mediated activity. Preferably, a sugar transporter family domain includes a polypeptide having an amino acid sequence of about 350-550, 400-550, or more preferably, about 411 or 521 amino acid residues and a sugar transporter mediated activity. To identify the presence of a sugar transporter family domain in an 8099 and/or an 46455 protein, and make the determination that a protein of interest has a particular profile, the amino acid sequence of the protein may be searched against a database of known protein domains (e.g., the PFAM HMM database). A PFAM sugar transporter family domain has been assigned the PFAM Accession PF00083. A search was performed against the PFAM HMM database resulting in the identification of a sugar transporter family domain in the amino acid sequence of human 8099 (SEQ ID NO:2) at about residues 43-564 of SEQ ID NO:2. A search was performed against the PFAM HMM database resulting in the identification of a sugar transporter family domain in the amino acid sequence of human 46455 (SEQ ID NO:5) at about residues 58-487 of SEQ ID NO:5.

[0081] Preferably a “sugar transporter family domain” has a “sugar transporter mediated activity” as described herein. For example, a sugar transporter family domain may have the ability to bind a monosaccharide (e.g., D-glucose, D-fructose, D-galactose and/or mannose); the ability to transport a monosaccharide (e.g., D-glucose, D-fructose, D-galactose and/or mannose) in a constitutive manner or in response to stimuli (e.g., insulin) across a cell membrane (e.g., a liver cell membrane, fat cell membrane, muscle cell membrane, and/or blood cell membrane, such as an erythrocyte membrane); the ability to function as a neuronal transporter; the ability to mediate trans-epithelial movement; and/or the ability to modulate sugar homeostasis in a cell. Accordingly, identifying the presence of a “sugar transporter family domain” can include isolating a fragment of an 8099 and/or an 46455 molecule (e.g., an 8099 and/or an 46455 polypeptide) and assaying for the ability of the fragment to exhibit one of the aforementioned sugar transporter mediated activities.

[0082] A description of the Pfam database can be found in Sonhammer et al. (1997) Proteins 28:405-420 and a detailed description of HMMs can be found, for example, in Gribskov et al.(1990) Meth. Enzymol. 183:146-159; Gribskov et al.(1987) Proc. Natl. Acad. Sci. USA 84:4355-4358; Krogh et al. (994) J. Mol. Biol. 235:1501-1531; and Stultz et al. (1993) Protein Sci. 2:305-314, the contents of which are incorporated herein by reference.

[0083] In a preferred embodiment, the 8099 and/or 46455 molecules of the invention include at least one, preferably two, even more preferably at least three, four, five, six, seven, eight, nine, ten, eleven, or twelve transmembrane domain(s) and/or at least one sugar transporter family domain. In another preferred embodiment, the 8099 molecules of the invention include at least one, preferably two, even more preferably at least three, four, five, six, seven, eight, nine, ten, eleven, or twelve transmembrane domain(s), at least one sugar transporter family domain, at least one unique N-terminal domain, and/or at least one extended exofacial loop.

[0084] Isolated polypeptides of the present invention, preferably 8099 or 46455 polypeptides, have an amino acid sequence sufficiently identical to the amino acid sequence of SEQ ID NO:2 or 5 or are encoded by a nucleotide sequence sufficiently identical to SEQ ID NO:1, 3, 4 or 6. As used herein, the term “sufficiently identical” refers to a first amino acid or nucleotide sequence which contains a sufficient or minimum number of identical or equivalent (e.g., an amino acid residue which has a similar side chain) amino acid residues or nucleotides to a second amino acid or nucleotide sequence such that the first and second amino acid or nucleotide sequences share common structural domains or motifs and/or a common functional activity. For example, amino acid or nucleotide sequences which share common structural domains having at least 50%,55%,60%,65%,70%,75%,80%,85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homology or identity across the amino acid sequences of the domains and contain at least one and preferably two structural domains or motifs, are defined herein as sufficiently identical. Furthermore, amino acid or nucleotide sequences which share at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homology or identity and share a common functional activity are defined herein as sufficiently identical.

[0085] In a preferred embodiment, an 8099 and/or 46455 polypeptide includes at least one or more of the following domains: a transmembrane domain and/or a sugar transporter family domain, and has an amino acid sequence at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homologous or identical to the amino acid sequence of SEQ ID NO:2 or 5, or the amino acid sequences encoded by the DNA inserts of the plasmids deposited with ATCC as Accession Numbers ______ and/or ______. In yet another preferred embodiment, an 8099 and/or an 46455 polypeptide includes at least one or more of the following domains: a transmembrane domain and/or a sugar transporter family domain, and is encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a complement of a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4 or SEQ ID NO:6. In another preferred embodiment, an 8099 and/or an 46455 polypeptide includes at least one or more of the following domains: a transmembrane domain and/or a sugar transporter family domain, and has an 8099 and/or an 46455 activity.

[0086] As used interchangeably herein, an “8099 activity”, “46455 activity”, “biological activity of 8099”, “biological activity of 46455”, “functional activity of 8099” or “functional activity of 46455” refers to an activity exerted by an 8099 and/or 46455 polypeptide or nucleic acid molecule on an 8099 and/or 46455 responsive cell or tissue, or on an 8099 and/or 46455 polypeptide substrate, as determined in vivo, or in vitro, according to standard techniques. In one embodiment, an 8099 and/or 46455 activity is a direct activity, such as an association with an 8099- and/or 46455-target molecule. As used herein, a “substrate,” “target molecule,” or “binding partner” is a molecule with which an 8099 and/or 46455 polypeptide binds or interacts in nature, such that 8099- and/or 46455-mediated function is achieved. An 8099 and/or 46455 target molecule can be a non- 8099 and/or a non-46455 molecule or an 8099 and/or 46455 polypeptide or polypeptide of the present invention. In an exemplary embodiment, an 8099 and/or 46455 target molecule is an 8099 and/or 46455 ligand, e.g., a sugar transporter ligand such D-glucose, D-fructose, D-galactose, and/or mannose. Alternatively, an 8099 and/or 46455 activity is an indirect activity, such as a cellular signaling activity mediated by interaction of the 8099 and/or 46455 polypeptide with an 8099 and/or 46455 ligand. The biological activities of 8099 and/or 46455 are described herein. For example, the 8099 and/or 46455 polypeptides of the present invention can have one or more of the following activities: (1) bind a monosaccharide, e.g., D-glucose, D-fructose, D-galactose, and/or mannose, (2) transport monosaccharides across a cell membrane, (3) influence insulin and/or glucagon secretion, (4) maintain sugar homeostasis in a cell, (5) function as a neuronal transporter, and (6) mediate trans-epithelial movement in a cell. Moreover, in a preferred embodiment, 8099 and/or 46455 molecules of the present invention, 8099 and/or 46455 antibodies, 8099 and/or 46455 modulators are useful in at least one of the following: (1) modulation of insulin sensitivity; (2) modulation of blood sugar levels; (3) treatment of blood sugar level disorders (e.g., diabetes); and/or (4) modulation of insulin resistance.

[0087] The nucleotide sequence of the isolated human 8099 and 46455 cDNAs and the predicted amino acid sequences of the human 8099 and 46455 polypeptides are shown in FIGS. 1 and 8 and in SEQ ID NOs:1 and 2, and SEQ ID NOs:4 and 5, respectively. Plasmids containing the nucleotide sequences encoding human 8099 or 46455 were deposited with the American Type Culture Collection (ATCC), 10801 University Boulevard, Manassas, Va. 20110-2209, on _and assigned Accession Numbers or _______. These deposits will be maintained under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure. These deposits were made merely as a convenience for those of skill in the art and are not an admission that a deposit is required under 35 U.S.C. §112.

[0088] The human 8099 gene, which is approximately 2725 nucleotides in length, encodes a polypeptide which is approximately 617 amino acid residues in length. The human 46455 gene, which is approximately 2230 nucleotides in length, encodes a polypeptide which is approximately 528 amino acid residues in length. 54414 and 53763 Molecules of the Invention The family of 54414 and 53763 proteins of the present invention comprises at least one transmembrane domain, preferably at least 2 or 3 transmembrane domains, more preferably 4 or 5 transmembrane domains, and most preferably, 6 transmembrane domains. Amino acid residues 64-83, 104-127, 135-153, 161-173, 199-217, and 257-274 of the human 54414 protein (SEQ ID NO:8) are predicted to comprise transmembrane domains. Amino acid residues 230-248, 287-303, 314-335, 346-368, 382-402, and 451-473 of the human 53763 protein (SEQ ID NO:11) are predicted to comprise transmembrane domains.

[0089] In another embodiment, members of the 54414 and 53763 family of proteins include at least one “ion transport protein domain” in the protein or corresponding nucleic acid molecule. As used herein, the term “ion transport protein domain” includes a protein domain having at least about 150-310 amino acid residues and a bit score of at least 200 when compared against an ion transport protein domain Hidden Markov Model (HMM), e.g., PFAM Accession Number PF00520. Preferably, an ion transport protein domain includes a protein domain having an amino acid sequence of about 170-290, 190-270, 210-250, or more preferably about 173 or 191 amino acid residues. To identify the presence of an ion transport protein domain in a 54414 or 53763 protein, and make the determination that a protein of interest has a particular profile, the amino acid sequence of the protein is searched against a database of known protein motifs and/or domains (e.g., the HMM database). The ion transport protein domain (HMM) has been assigned the PFAM Accession number PF00520. A search was performed against the HMM database resulting in the identification of an ion transport protein domain in the amino acid sequence of human 54414 at about residues 104-277 of SEQ ID NO:8 and in the amino acid sequence of human 53763 about residues 281-472 of SEQ ID NO:11.

[0090] Preferably an ion transport protein domain is at least about 150-310 amino acid residues and has an “ion transport protein domain activity”, for example, the ability to interact with a 54414 or 53763 substrate or target molecule (e.g., a potassium ion) and/or to regulate 54414 or 53763 activity. Accordingly, identifying the presence of an “ion transport protein domain” can include isolating a fragment of a 54414 or 53763 molecule (e.g., a 54414 or 53763 polypeptide) and assaying for the ability of the fragment to exhibit one of the aforementioned ion transport protein domain activities.

[0091] In another embodiment, members of the 54414 and 53763 family of proteins include at least one “K⁺ channel tetramerisation domain” in the protein or corresponding nucleic acid molecule. As used herein, the term “K channel tetramerisation domain” includes a protein domain having at least about 70-230 amino acid residues and a bit score of at least 80 when compared against a K⁺ channel tetramerisation domain Hidden Markov Model (HMM), e.g., PFAM Accession Number PF02214. Preferably, a K⁺ channel tetramerisation domain includes a protein domain having an amino acid sequence of about 90-210, 110-190, 130-170, or more preferably about 149 amino acid residues, and a bit score of at least 100, 120, 140, or more preferably, 156.7. To identify the presence of a K⁺ channel tetramerisation domain in a 54414 or 53763 protein, and make the determination that a protein of interest has a particular profile, the amino acid sequence of the protein is searched against a database of known protein motifs and/or domains (e.g., the HMM database). The K⁺ channel tetramerisation domain (HMM) has been assigned the PFAM Accession number PF02214. A search was performed against the HMM database resulting in the identification of a K⁺ channel tetramerisation domain in the amino acid sequence of human 53763 at about residues 8-156 of SEQ ID NO:11.

[0092] Preferably a K⁺ channel tetramerisation domain is at least about 70-230 amino acid residues and has an “K⁺ channel tetramerisation domain activity”, for example, the ability to interact with one or more potassium channel subunits (e.g., 54414 or 53763 molecules, or non-54414 or 53763 potassium channel subunits), the ability to regulate assembly of a 54414 or 53763 molecule into a potassium channel tetramer, and/or to regulate 54414 or 3s 53763 activity. Accordingly, identifying the presence of an “K⁺ channel tetramerisation domain” can include isolating a fragment of a 54414 or 53763 molecule (e.g., a 54414 or 53763 polypeptide) and assaying for the ability of the fragment to exhibit one of the aforementioned K⁺ channel tetramerisation domain activities.

[0093] In another embodiment, a 54414 or 53763 protein of the present invention is identified based on the presence of an “ATP/GTP-binding sit motif A (P-loop) motif”, referred to alternatively herein as a “P-loop motif”, in the protein or corresponding nucleic acid molecule. Preferably, a P-loop motif includes a protein motif which is about 4-15, 5-13, 6-11, 7-9, or preferably about 8 amino acid residues. The P-loop motif functions in binding ATP and/or GTP via interaction with the phosphate groups of the nucleotide and has been assigned Prosite™ Accession Number PS00017. To identify the presence of a P-loop motif in a 54414 or 53763 protein, and to make the determination that a protein of interest has a particular profile, the amino acid sequence of the protein may be searched against a database of known protein domains or motifs (e.g., the Prosite™ database) using the default parameters (available at the ProSite website). A search was performed against the ProSite database resulting in the identification of a P-loop motif in the amino acid sequence of human 54414 (SEQ ID NO:8) at about residues 1007-1014.

[0094] In another embodiment, a 54414 or 53763 protein of the present invention is identified based on the presence of a “pore domain”, alternatively referred to herein as a “P-region domain”, in the protein or corresponding nucleic acid molecule. As used interchangeably herein, the terms “pore domain” and “P-region domain” include a protein domain having about 10-30, 12-28, 13-25, 14-24, 15-23, or preferably about 16-22 amino acid residues, which is involved in lining the potassium channel pore. A pore domain is typically found between transmembrane domains of potassium channels and is believed to be a major determinant of ion selectivity in potassium channels. Preferably, a pore domain includes a potassium channel signature motif, as defined herein. Pore domains are described in, for example, Warmke et al. (1991) Science 252:1560-1562; Zagotta W. N. et al. (1996) Annu. Rev. Neurosci. 19:235-63; Pongs, O. (1993) J. Membr. Biol. 136:1-8; Heginbotham et al. (1994) Biophys. J. 66:1061-1067; Mackinnon, R. (1995) Neuron 14:889-892; and Pascual et al. (1995) Neuron 14:1055-1063), the contents of which are incorporated herein by reference. A pore domain was identified in the amino acid sequence of human 54414 at about residues 229-250 of SEQ ID NO:8. A pore domain was identified in the amino acid sequence of human 53763 at about residues 426-441 of SEQ ID NO:11.

[0095] In a further embodiment, a 54414 or 53763 protein of the present invention is identified based on the presence of a “potassium channel signature sequence motif” in the protein or corresponding nucleic acid molecule. As used herein, the term “potassium channel signature sequence motif” includes a protein motif which is diagnostic for potassium channels. Preferably, a potassium channel signature sequence motif has the consensus sequence T-X-X-T-X-G-hydrophobic-G (see Joiner, W. J. et al. (1998) Nat. Neurosei. 1:462-469 and references cited therein), wherein “X” indicates any amino acid residue, and “hydrophobic” indicates any hydrophobic amino acid residue. Preferably, a potassium channel signature sequence motif is included within a pore domain and includes at least 1, 2, 3, 4, 5, 6, 7, or more preferably, 8 amino acid residues that match the consensus sequence for a potassium channel signature sequence motif. A potassium channel signature sequence motif was identified in the amino acid sequence of human 54414 at about residues 239-246 of SEQ ID NO:8. A potassium channel signature sequence motif was identified in the amino acid sequence of human 53763 at about residues 436-441 of SEQ ID NO:11.

[0096] In still another embodiment, a 54414 or 53763 protein of the present invention is identified based on the presence of a “voltage sensor motif”, alternatively referred to simply as a “voltage sensor”, in the protein or the corresponding nucleic acid molecule. As used interchangeably herein, the terms “voltage sensor motif” and “voltage sensor” include a protein motif having about 10-30, 11-26, 12-24, 13-22, 14-20, 15-18, or more preferably 16 amino acid residues, which is involved in sensing voltage differences between the two sides of the plasma membrane of a cell. Preferably, a voltage sensor motif includes at least 1, 2, 3, 4, 5, or more preferably, 6 positively charged amino acid residues, which are preferably spaced apart by at least 1, or preferably 2, non-positively charged amino acid residues. Preferably, a voltage sensor motif is included within and/or overlaps with a transmembrane domain, more preferably the fourth transmembrane, of the 54414 or 53763 protein in which it is found. A voltage sensor motif was identified in the amino acid sequence of human 53763 at about residues 348-363 of SEQ ID NO:8. The positively charged amino acid residues of the human 53763 voltage sensor were identified at about residues 348, 351, 354, 357, 360, and 363 of SEQ ID NO:8. No voltage sensor was identified in human 54414.

[0097] Isolated proteins of the present invention, preferably 54414 or 53763 proteins, have an amino acid sequence sufficiently homologous to the amino acid sequence of SEQ ID NO:8 or SEQ ID NO:11, or are encoded by a nucleotide sequence sufficiently homologous to SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:12. Amino acid or nucleotide sequences which share common structural domains having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homology or identity across the amino acid sequences of the domains and contain at least one and preferably two structural domains or motifs, are defined herein as sufficiently homologous. Furthermore, amino acid or nucleotide sequences which share at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homology or identity and share a common functional activity are defined herein as sufficiently homologous.

[0098] In a preferred embodiment, a 54414 or 53763 protein includes at least one or more of the following domains or motifs: a transmembrane domain, an ion transport protein domain, a K⁺ channel tetramerisation domain, a P-loop motif, a pore domain, a potassium channel signature sequence motif, and/or a voltage sensor motif. and has an amino acid sequence at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homologous or identical to the amino acid sequence of SEQ ID NO:8 or 11, or the amino acid sequence encoded by the DNA insert of the plasmid deposited with ATCC as Accession Number ______ or ______. In yet another preferred embodiment, a 54414 or 53763 protein includes at least one or more of the following domains or motifs: a transmembrane domain, an ion transport protein domain, a K⁺ channel tetramerisation domain, a P-loop motif, a pore domain, a potassium channel signature sequence motif, and/or a voltage sensor motif, and is encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a complement of a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:7, 9, 10, or 12. In another preferred embodiment, a 54414 or 53763 protein includes at least one or more of the following domains or motifs: a transmembrane domain, an ion transport protein domain, a K⁺ channel tetramerisation domain, a P-loop motif, a pore domain, a potassium channel signature sequence motif, and/or a voltage sensor motif, and has a 54414 or 53763 activity.

[0099] As used interchangeably herein, a “54414 or 53763 activity”, “biological activity of 54414 or 53763” or “functional activity of 54414 or 53763”, includes an activity exerted or mediated by a 54414 or 53763 protein, polypeptide or nucleic acid molecule when expressed in a cell or on a membrane, as determined in vivo or in vitro, according to standard techniques. In one embodiment, a 54414 or 53763 activity is a direct activity, such as transport of a 54414 or 53763 substrate (e.g., a potassium ion). In another embodiment, a 54414 or 53763 activity is an indirect activity mediated, for example, by interaction of a 54414 or 53763 molecule with a 54414 or 53763 target molecule or binding partner. As used herein, a “target molecule” or “binding partner” is a molecule with which a 54414 or 53763 protein binds or interacts in nature, such that function of the target molecule or binding partner is modulated. In an exemplary embodiment, a 54414 or 53763 target molecule or binding partner is a 54414 or 53763 polypeptide or a non-54414 or 53763 potassium channel subunit.

[0100] In a preferred embodiment, a 54414 or 53763 activity is at least one of the following activities: (i) interaction with a 54414 or 53763 substrate (e.g., a potassium ion or a cyclic nucleotide); (ii) conductance or transport of a 54414 or 53763 substrate across a cellular membrane; (iii) interaction with a second protein (e.g., a second 54414 or 53763 subunit or a non-54414 or 53763 potassium channel subunit); (iv) modulation (e.g., maintenance and/or rectification) of membrane potentials; (v) regulation of target molecule availability or activity; (vi) modulation of intra- or intercellular signaling and/or gene transcription (e.g., either directly or indirectly); (viii) generation of outwardly rectifying currents; (viii) modulation of membrane excitability; (ix) modulation of the release of neurotransmitters; (x) regulation of contractility (e.g., of smooth muscle cells), secretion, and/or synaptic transmission; and/or (xi) modulation of processes which underlie learning and memory.

[0101] Preferred activities of 54414 further include at least one of the following activities: (i) interaction with maxi-K potassium channels (i.e., large conductance channels, in particular Slo); (ii) modulation of maxi-K potassium channel activity (e.g., Slo-mediated activities); (iii) generation of intermediate conductance channels; and/or (iv) regulation of contractility (e.g., of smooth muscle cells), secretion, and/or synaptic transmission, in particular, via modulation of Slo.

[0102] Preferred activities of 53763 further include at least one of the following activities: (i) interaction with Shaker (Sh) potassium channels and/or channel subunits; (ii) modulation of Shaker (Sh) potassium channel activity (e.g., termination of prolonged membrane depolarization; (iii) modulation of high voltage activating channel activity and/or inactivating channel activity, and the like.

[0103] The nucleotide sequence of the isolated human 54414 cDNA and the predicted amino acid sequence encoded by the 54414 cDNA are shown in FIGS. 12A-C and in SEQ ID NOs:7 and 8, respectively. A plasmid containing the human 54414 cDNA was deposited with the American Type Culture Collection (ATCC), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______ and assigned Accession Number ______. This deposit will be maintained under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure. This deposit were made merely as a convenience for those of skill in the art and is not an admission that a deposit is required under 35 U.S.C. §112.

[0104] The human 54414 gene, which is approximately 4632 nucleotides in length, encodes a protein having a molecular weight of approximately 123 kD and which is approximately 1118 amino acid residues in length.

[0105] The nucleotide sequence of the isolated human 53763 cDNA and the predicted amino acid sequence encoded by the 53763 cDNA are shown in FIGS. 16A-C and in SEQ ID NOs:10 and 11, respectively. A plasmid containing the human 53763 cDNA was deposited with the American Type Culture Collection (ATCC), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______ and assigned Accession Number ______. This deposit will be maintained under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure. This deposit were made merely as a convenience for those of skill in the art and is not an admission that a deposit is required under 35 U.S.C. §112.

[0106] The human 53763 gene, which is approximately 2847 nucleotides in length, encodes a protein having a molecular weight of approximately 70.2 kD and which is approximately 3s 638 amino acid residues in length.

[0107] 67076, 67102, 44181, 67084FL, and 67084alt Molecules of the Invention

[0108] The 67076, 67102, 44181, 67084FL, and 67084alt polypeptides comprise at least one “transmembrane domain” and preferably eight, nine, or ten transmembrane domains. A MEMSAT analysis and a structural, hydrophobicity, and antigenicity analysis also resulted in the identification of ten transmembrane domains in the amino acid sequence of human 67076 (SEQ ID NO:14) at about residues 57-77, 84-105, 292-313, 345-365, 863-883, 905-926, 956-977, 989-1009, 1021-1041, and 1060-1087. A MEMSAT analysis and a structural, hydrophobicity, and antigenicity analysis resulted in the identification of ten transmembrane domains in the amino acid sequence of human 67102 (SEQ ID NO:17) at about residues 98-115, 122-140, 322-344, 366-390, 582-601, 752-770, 1145-1166, 1225-1246, 1253-1276, and 1298-1317. A MEMSAT analysis and a structural, hydrophobicity, and antigenicity analysis resulted in the identification of ten transmembrane domains in the amino acid sequence of human 44181 (SEQ ID NO:20) at about residues 56-72, 87-103, 290-311, 343-363, 878-898, 911-931, 961-982, 995-1015, 1027-1047, and 1062-1086. A MEMSAT analysis and a structural, hydrophobicity, and antigenicity analysis resulted in the identification of ten transmembrane domains in the amino acid sequence of human 67084FL (SEQ ID NO:23) at about residues 104-120, 124-144, 331-350, 357-374, 887-903, 912-931, 961-983, 990-1008, 1015-1035, and 1043-1067. A MEMSAT analysis and a structural, hydrophobicity, and antigenicity analysis resulted in the identification of ten transmembrane domains in the amino acid sequence of human 67084alt (SEQ ID NO:26) at about residues 104-120, 124-144, 331-350, 357-379, 887-903, 912-931, 961-983, 990-1008, 1015-1035, and 1054-1078.

[0109] The family of 67076, 67102, 44181, 67084FL, or 67084alt proteins of the present invention also comprises at least one “extramembrane domain” in the protein or corresponding nucleic acid molecule. As used herein, an “extramembrane domain” includes a domain having greater than 20 amino acid residues that is found between transmembrane domains, preferably on the cytoplasmic side of the plasma membrane, and does not span or traverse the plasma membrane. An extramembrane domain preferably includes at least one, two, three, four or more motifs or consensus sequences characteristic of P-type ATPases, i.e., includes one, two, three, four, or more “P-type ATPase consensus sequences or motifs”. As used herein, the phrase “P-type ATPase consensus sequences or motifs” includes any consensus sequence or motif known in the art to be characteristic of P-type ATPases, including, but not limited to, the P-type ATPase sequence 1 motif (as defined herein), the P-type ATPase sequence 2 motif (as defined herein), the P-type ATPase sequence 3 motif (as defined herein), and the E1-E2 ATPases phosphorylation site (as defined herein).

[0110] In one embodiment, the family of 67076, 67102, 44181, 67084FL, or 67084alt proteins of the present invention comprises at least one “N-terminal” large extramembrane domain in the protein or corresponding nucleic acid molecule. As used herein, an “N-terminal” large extramembrane domain is found in the N-terminal ⅓^(rd) of the protein, preferably between the second and third transmembrane domains of a 67076, 67102, 44181, 67084FL, or 67084alt protein and includes about 60-300, 80-280, 100-260, 120-240, 140-220, 160-200, or preferably, 180, 185, or 186 amino acid residues. In a preferred embodiment, an N-terminal large extramembrane domain includes at least one P-type ATPase sequence 1 motif (as described herein). An N-terminal large extramembrane domain was identified in the amino acid sequence of human 67076 at about residues 106-291 of SEQ ID NO:14. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 67102 at about residues 141-321 of SEQ ID NO:17. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 44181 at about residues 104-289 of SEQ ID NO:20. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 67084FL at about residues 145-330 of SEQ ID NO:23. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 67087alt at about residues 145-330 of SEQ ID NO:26.

[0111] The family of 67076, 67102, 44181, 67084FL, or 67084alt proteins of the present invention also comprises at least one “C-terminal” large extramembrane domain in the protein or corresponding nucleic acid molecule. As used herein, a “C-terminal” large extramembrane domain is found in the C-terminal ⅔^(rds) of the protein, preferably between the fourth and fifth transmembrane domains of a 67076, 67102, 44181, 67084FL, or 67084alt protein and includes about 150-1000, 300-900, 370-850, 400-820, 430-790, 460-760, 430-730, 460-700, 430-670, 460-640, 430-610, 490-580, 510-550, or preferably, 190, 506, or 523 amino acid residues. In a preferred embodiment, a C-terminal large extramembrane domain includes at least one or more of the following motifs: a P-type ATPase sequence 2 motif (as described herein), a P-type ATPase sequence 3 motif (as defined herein), and/or an E1-E2 ATPases phosphorylation site (as defined herein). A C-terminal large extramembrane domain was identified in the amino acid sequence of human 67076 at about residues 366-862 of SEQ ID NO:14. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 67102 at about residues 391-581 of SEQ ID NO:17. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 44181 at about residues 364-877 of SEQ ID NO:20. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 67084FL at about residues 380-886 of SEQ ID NO:23. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 67084alt at about residues 380-886 of SEQ ID NO:26.

[0112] In another embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein or 67076, 67102, 44181, 67084FL, or 67084alt extramembrane domain is characterized by at least one “P-type ATPase sequence 1 motif” in the protein or corresponding nucleic acid sequence. As used herein, a “P-type ATPase sequence 1 motif” is a conserved sequence motif diagnostic for P-type ATPases (Tang, X. et al. (1996) Science 272:1495-1497; Fagan, M. J. and Saier, M. H. (1994) J. Mol. Evol. 38:57). Amino acid residues of the P-type ATPase sequence 1 motif are involved in the coupling of ATP hydrolysis with transport (e.g., transport of phospholipids). The consensus sequence for a P-type ATPase sequence 1 motif is [DNS]-[QENR]-[SA]-[LIVSAN]-[LIV]-[TSN]-G-E-[SN] (SEQ ID NO:37). The use of amino acids in brackets indicates that the amino acid at the indicated position may be any one of the amino acids within the brackets, e.g., [SA] indicates any of one of either S (serine) or A (alanine). In a preferred embodiment, a P-type ATPase sequence 1 motif is contained within an N-terminal large extramembrane domain. In another preferred embodiment, a P-type ATPase sequence I motif in the 67076, 67102, 44181, 67084FL, or 67084alt proteins of the present invention has at least 1, 2, 3, or preferably 4 amino acid resides which match the consensus sequence for a P-type ATPase sequence 1 motif. A P-type ATPase sequence 1 motif was identified in the amino acid sequence of human 67076 at about residues 173-181 of SEQ ID NO:14. A P-type ATPase sequence 1 motif was identified in the amino acid sequence of human 67102 at about residues 208-216 of SEQ ID NO:17. A P-type ATPase sequence 1 motif was identified in the amino acid sequence of human 44181 at about residues 173-181 of SEQ ID NO:20. A P-type ATPase sequence 1 motif was identified in the amino acid sequence of human 67084FL at about residues 213-221 of SEQ ID NO:23. A P-type ATPase sequence 1 motif was identified in the amino acid sequence of human 67084alt at about residues 213-221 of SEQ ID NO:26.

[0113] In another embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein or 67076, 67102, 44181, 67084FL, or 67084alt extramembrane domain is characterized by at least one “P-type ATPase sequence 2 motif” in the protein or corresponding nucleic acid sequence. As used herein, a “P-type ATPase sequence 2 motif” is a conserved sequence motif diagnostic for P-type ATPases (Tang, X. et al. (1996) Science 272:1495-1497; Fagan, M. J. and Saier, M. H. (1994) J. Mol. Evol. 38:57). Preferably, a P-type ATPase sequence 2 motif overlaps with and/or includes an E1-E2 ATPases phosphorylation site (as defined herein). The consensus sequence for a P-type ATPase sequence 2 motif is [LIV]-[CAML]-[STFL]-D-K-T-G-T-[LI]-T (SEQ ID NO:38). The use of amino acids in brackets indicates that the amino acid at the indicated position may be any one of the amino acids within the brackets, e.g., [LI] indicates any of one of either L (leucine) or I (isoleucine). In a preferred embodiment, a P-type ATPase sequence 2 motif is contained within a C-terminal large extramembrane domain. In another preferred embodiment, a P-type ATPase sequence 2 motif in the 67076, 67102, 44181, 67084FL, or 67084alt proteins of the present invention has at least 1, 2, 3, 4, 5, 6, 7, 8, or more preferably 9 amino acid resides which match the consensus sequence for a P-type ATPase sequence 2 motif. A P-type ATPase sequence 2 motif was identified in the amino acid sequence of human 67076 at about residues 406-415 of SEQ ID NO:14. A P-type ATPase sequence 2 motif was identified in the amino acid sequence of human 67102 at about residues 435-444 of SEQ ID NO:17. A P-type ATPase sequence 2 motif was identified in the amino acid sequence of human 44181 at about residues 404-413 of SEQ ID NO:20. A P-type ATPase sequence 2 motif was identified in the amino acid sequence of human 67084FL at about residues 413-422 of SEQ ID NO:23. A P-type ATPase sequence 2 motif was identified in the amino acid sequence of human 67084alt at about residues 413-422 of SEQ ID NO:26.

[0114] In yet another embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein or 67076, 67102, 44181, 67084FL, or 67084alt extramembrane domain is characterized by at least one “P-type ATPase sequence 3 motif” in the protein or corresponding nucleic acid sequence. As used herein, a “P-type ATPase sequence 3 motif” is a conserved sequence motif diagnostic for P-type ATPases (Tang, X. et al. (1996) Science 272:1495-1497; Fagan, M. J. and Saier, M. H. (1994) J. Mol. Evol. 38:57). Amino acid residues of the P-type ATPase sequence 3 motif are involved in ATP binding. The consensus sequence for a P-type ATPase sequence 3 motif is [TIV]-G-D-G-X-N-D-[ASG]-P-[ASV]-L (SEQ ID NO:39). X indicates that the amino acid at the indicated position may be any amino acid (i.e., is not conserved). The use of amino acids in brackets indicates that the amino acid at the indicated position may be any one of the amino acids within the brackets, e.g, [TIV] indicates any of one of either T (threonine), I (isoleucine), or V (valine). In a preferred embodiment, a P-type ATPase sequence 3 motif is contained within a C-terminal large extramembrane domain. In another preferred embodiment, a P-type ATPase sequence 3 motif in the 67076, 67102, 44181, 67084FL, or 67084alt proteins of the present invention has at least 1, 2, 3, 4, 5, 6, or more preferably 7 amino acid resides (including the amino acid at the position indicated by “X”) which match the consensus sequence for a P-type ATPase sequence 3 motif. A P-type ATPase sequence 3 motif was identified in the amino acid sequence of human 67076 at about residues 813-824 of SEQ ID NO:14. A P-type ATPase sequence 3 motif was identified in the amino acid sequence of human 67102 at about residues 1054-1064 of SEQ ID NO:17. A P-type ATPase sequence 3 motif was identified in the amino acid sequence of human 44181 at about residues 819-829 of SEQ ID NO:20. A P-type ATPase sequence 3 motif was identified in the amino acid sequence of human 67084FL at about residues 820-830 of SEQ ID NO:23. A P-type ATPase sequence 3 motif was identified in the amino acid sequence of human 67084alt at about residues 820-830 of SEQ ID NO:26.

[0115] In another embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein of the present invention is identified based on the presence of an “E1-E2 ATPases phosphorylation site” (alternatively referred to simply as a “phosphorylation site”) in the protein or corresponding nucleic acid molecule. An E1-E2 ATPases phosphorylation site functions in accepting a phosphate moiety and has the amino acid sequence DKTGT (amino acid residues 4-8 of SEQ ID NO:38), and can be included within the E1-E2 ATPase phosphorylation site consensus sequence: D-K-T-G-T-[LIVM]-[TI] (SEQ ID NO:41), wherein D is phosphorylated. The use of amino acids in brackets indicates that the amino acid at the indicated position may be any one of the amino acids within the brackets, e.g., [TI] indicates any of one of either T (threonine) or I (isoleucine). The E1-E2 ATPases phosphorylation site consensus sequence has been assigned ProSite Accession Number PS00154. To identify the presence of an E1-E2 ATPases phosphorylation site consensus sequence in a 67076, 67102, 44181, 67084FL, or 67084alt protein, and to make the determination that a protein of interest has a particular profile, the amino acid sequence of the protein may be searched against a database of known protein motifs (e.g., the ProSite database) using the default parameters (available at the Prosite website). A search was performed against the ProSite database resulting in the identification of an E1-E2 ATPases phosphorylation site consensus sequence in the amino acid sequence of human 67076 (SEQ ID NO:14) at about residues 409-415. A search was performed against the ProSite database resulting in the identification of an E1-E2 ATPases phosphorylation site consensus sequence in the amino acid sequence of human 67102 (SEQ ID NO:17) at about residues 438-444. A search was performed against the ProSite database resulting in the identification of an E1-E2 ATPases phosphorylation site consensus sequence in the amino acid sequence of human 44181 (SEQ ID NO:20) at about residues 407-413. A search was performed against the ProSite database resulting in the identification of an E1-E2 ATPases phosphorylation site consensus sequence in the amino acid sequence of human 67084FL (SEQ ID NO:23) at about residues 416-422. A search was performed against the ProSite database resulting in the identification of an E1-E2 ATPases phosphorylation site consensus sequence in the amino acid sequence of human 67084alt (SEQ ID NO:26) at about residues 416-422.

[0116] Preferably an E1-E2 ATPases phosphorylation site has a “phosphorylation site activity,” for example, the ability to be phosphorylated; to be dephosphorylated; to regulate the E1-E2 conformational change of the phospholipid transporter in which it is contained; to regulate transport of phospholipids (e.g., aminophospholipids such as phosphatidylserine and phosphatidylethanolamine, choline phospholipids such as phosphatidylcholine and sphingomyelin, and bile acids) across a cellular membrane by the 67076, 67102, 44181, 67084FL, or 67084alt protein in which it is contained; and/or to regulate the activity (as defined herein) of the 67076, 67102, 44181, 67084FL, or 67084alt protein in which it is contained. Accordingly, identifying the presence of an “E1-E2 ATPases phosphorylation site” can include isolating a fragment of a 67076, 67102, 44181, 67084FL, or 67084alt molecule (e.g., a 67076, 67102, 44181, 67084FL, or 67084alt polypeptide) and assaying for the ability of the fragment to exhibit one of the aforementioned phosphorylation site activities.

[0117] In another embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein of the present invention may also be identified based on its ability to adopt an E1 conformation or an E2 conformation. As used herein, an “E1 conformation” of a 67076, 67102, 44181, 67084FL, or 67084alt protein includes a 3-dimensional conformation of a 67076, 67102, 44181, 67084FL, or 67084alt protein which does not exhibit 67076, 67102, 44181, 67084FL, or 67084alt activity (e.g., the ability to transport phospholipids), as defined herein. An E1 conformation of a 67076, 67102, 44181, 67084FL, or 67084alt protein usually occurs when the 67076, 67102, 44181, 67084FL, or 67084alt protein is unphosphorylated. As used herein, an “E2 conformation” of a 67076, 67102, 44181, 67084FL, or 67084alt protein includes a 3-dimensional conformation of a 67076, 67102, 44181, 67084FL, or 67084alt protein which exhibits 67076, 67102, 44181, 67084FL, or 67084alt activity (e.g., the ability to transport phospholipids), as defined herein. An E2 conformation of a 67076, 67102, 44181, 67084FL, or 67084alt protein usually occurs when the 67076, 67102, 44181, 67084FL, or 67084alt protein is phosphorylated.

[0118] In still another embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein of the present invention is identified based on the presence of “phospholipid transporter specific” amino acid residues. As used herein, “phospholipid transporter specific” amino acid residues are amino acid residues specific to the class of phospholipid transporting P-type ATPases (as defined in Tang, X. et al. (1996) Science 272:1495-1497). Phospholipid transporter specific amino acid residues are not found in those P-type ATPases which transport molecules which are not phospholipids (e.g., cations). For example, phospholipid transporter specific amino acid residues are found at the first, second, and fifth positions of the P-type ATPase sequence 1 motif. In phospholipid transporting P-type ATPases, the first position of the P-type ATPase sequence 1 motif is preferably E (glutamic acid), the second position is preferably T (threonine), and the fifth position is preferably L (leucine). A phospholipid transporter specific amino acid residue is further found at the second position of the P-type ATPase sequence 2 motif. In phospholipid transporting P-type ATPases, the second position of the P-type ATPase sequence 2 motif is preferably F (phenylalanine). Phospholipid transporter specific amino acid residues are still further found at the first, tenth, and eleventh positions of the P-type ATPase sequence 3 motif. In phospholipid transporting P-type ATPases, the first position of the P-type ATPase sequence 3 motif is preferably I (isoleucine), the tenth position is preferably M (methionine), and the eleventh position is preferably I (isoleucine).

[0119] Phospholipid transporter specific amino acid residues were identified in the amino acid sequence of human 67076 (SEQ ID NO:14) at about residues 174 and 177 (within the P-type ATPase sequence 1 motif), at about residue 407 (within the P-type ATPase sequence 2 motif), and at about residues 813, 823, and 824 (within the P-type ATPase sequence 3 motif).

[0120] Phospholipid transporter specific amino acid residues were identified in the amino acid sequence of human 67102 (SEQ ID NO:17) at about residues 208, 209, and 212 (within the P-type ATPase sequence 1 motif), at about residue 436 (within the P-type ATPase sequence 2 motif), and at about residues 1054, 1063, and 1064 (within the P-type ATPase sequence 3 motif).

[0121] Phospholipid transporter specific amino acid residues were identified in the amino acid sequence of human 44181 (SEQ ID NO:20) at about residues 174 and 177 (within the P-type ATPase sequence 1 motif), at about residue 405 (within the P-type ATPase sequence 2 motif), and at about residues 819, 828, and 829 (within the P-type ATPase sequence 3 motif).

[0122] Phospholipid transporter specific amino acid residues were identified in the amino acid sequence of human 67084FL (SEQ ID NO:23) at about residues 214 and 217 (within the P-type ATPase sequence 1 motif) and at about residues 820, 829, and 830 (within the P-type ATPase sequence 3 motif).

[0123] Phospholipid transporter specific amino acid residues were identified in the amino acid sequence of human 67084alt (SEQ ID NO:26) at about residues 214 and 217 (within the P-type ATPase sequence 1 motif), and at about residues 820, 829, and 830 (within the P-type ATPase sequence 3 motif).

[0124] Isolated polypeptides of the present invention, preferably 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, have an amino acid sequence sufficiently identical to the amino acid sequence of SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26 or are encoded by a nucleotide sequence sufficiently identical to SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:27. For example, amino acid or nucleotide sequences which share common structural domains having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homology or identity across the amino acid sequences of the domains and contain at least one and preferably two structural domains or motifs, are defined herein as sufficiently identical. Furthermore, amino acid or nucleotide sequences which share at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homology or identity and share a common functional activity are defined herein as sufficiently identical.

[0125] In a preferred embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein includes at least one or more of the following domains, sites, or motifs: a transmembrane domain, an N-terminal large extramembrane domain, a C-terminal large extramembrane domain, an E1-E2 ATPases phosphorylation site, a P-type ATPase sequence 1 motif, a P-type ATPase sequence 2 motif, a P-type ATPase sequence 3 motif, and/or one or more phospholipid transporter specific amino acid resides, and has an amino acid sequence at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more homologous or identical to the amino acid sequence of SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, or the amino acid sequence encoded by the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______. In yet another preferred embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein includes at least one or more of the following domains, sites, or motifs: a transmembrane domain, an N-terminal large extramembrane domain, a C-terminal large extramembrane domain, an E1-E2 ATPases phosphorylation site, a P-type ATPase sequence 1 motif, a P-type ATPase sequence 2 motif, a P-type ATPase sequence 3 motif, and/or one or more phospholipid transporter specific amino acid resides, and is encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under stringent hybridization conditions to a complement of a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:27. In another preferred embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt protein includes at least one or more of the following domains, sites, or motifs: a transmembrane domain, an N-terminal large extramembrane domain, a C-terminal large extramembrane domain, an E1-E2 ATPases phosphorylation site, a P-type ATPase sequence 1 motif, a P-type ATPase sequence 2 motif, a P-type ATPase sequence 3 motif, and/or one or more phospholipid transporter specific amino acid resides, and has a 67076, 67102, 44181, 67084FL, or 67084alt activity.

[0126] As used interchangeably herein, a “phospholipid transporter activity” or a “67076, 67102, 44181, 67084FL, or 67084alt activity” includes an activity exerted or mediated by a 67076, 67102, 44181, 67084FL, or 67084alt protein, polypeptide or nucleic acid molecule on a 67076, 67102, 44181, 67084FL, or 67084alt responsive cell or on a 67076, 67102, 44181, 67084FL, or 67084alt substrate, as determined in vivo or in vitro, according to standard techniques. In one embodiment, a phospholipid transporter activity is a direct activity, such as an association with a 67076, 67102, 44181, 67084FL, or 67084alt target molecule. As used herein, a “target molecule” or “binding partner” is a molecule with which a 67076, 67102, 44181, 67084FL, or 67084alt protein binds or interacts in nature, such that 67076, 67102, 44181, 67084FL, or 67084alt-mediated function is achieved. In an exemplary embodiment, a 67076, 67102, 44181, 67084FL, or 67084alt target molecule is a 67076, 67102, 44181, 67084FL, or 67084alt substrate (e.g., a phospholipid, ATP, or a non-67076, 67102, 44181, 67084FL, or 67084alt protein). A phospholipid transporter activity can also be an indirect activity, such as a cellular signaling activity mediated by interaction of the 67076, 67102, 44181, 67084FL, or 67084alt protein with a 67076, 67102, 44181, 67084FL, or 67084alt substrate.

[0127] In a preferred embodiment, a phospholipid transporter activity is at least one of the following activities: (i) interaction with a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., a phospholipid, ATP, or a non-67076, 67102, 44181, 67084FL, or 67084alt protein); (ii) transport of a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., an aminophospholipid such as phosphatidylserine or phosphatidylethanolamine) from one side of a cellular membrane to the other; (iii) the ability to be phosphorylated or dephosphorylated; (iv) adoption of an E1 conformation or an E2 conformation; (v) conversion of a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule to a product (e.g., hydrolysis of ATP); (vi) interaction with a second non-67076, 67102, 44181, 67084FL, or 67084alt protein; (vii) modulation of substrate or target molecule location (e.g., modulation of phospholipid location within a cell and/or location with respect to a cellular membrane); (viii) maintenance of aminophospholipid gradients; (ix) modulation of intra- or intercellular signaling and/or gene transcription (e.g., either directly or indirectly); and/or (x) modulation of cellular proliferation, growth, differentiation, apoptosis, absorption, or secretion.

[0128] The nucleotide sequence of the isolated human 67076, 67102, 44181, 67084FL, or 67084alt cDNA and the predicted amino acid sequence of the human 67076, 67102, 44181, 67084FL, or 67084alt polypeptides are shown in FIGS. 20A-E, 24A-E, 28A-E, 32A-E, and 36A-E, and in SEQ ID NOs: 13 and 14, SEQ ID NOs: 16 and 17, SEQ ID NOs: 19 and 20, SEQ ID NOs:22 and 23, and SEQ ID NOs:25 and 26, respectively. Plasmids containing the nucleotide sequence encoding human 67076, human 67102, human 44181, human 67084FL, and/or human 67084alt were deposited with the American Type Culture Collection (ATCC), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, ______, ______, ______, and ______, respectively, and assigned Accession Numbers ______, ______, ______, ______, and ______, respectively. These deposits will be maintained under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure. These deposit were made merely as a convenience for those of skill in the art and are not admissions that a deposit is required under 35 U.S.C. §112.

[0129] The human 67076 gene, which is approximately 6582 nucleotides in length, encodes a polypeptide which is approximately 1129 amino acid residues in length. The human 67102 gene, which is approximately 6074 nucleotides in length, encodes a polypeptide which is approximately 1426 amino acid residues in length. The human 44181 gene, which is approximately 7221 nucleotides in length, encodes a polypeptide which is approximately 1177 amino acid residues in length. The human 67084FL gene, which is approximately 4198 nucleotides in length, encodes a polypeptide which is approximately 1084 amino acid residues in length. The human 67084alt gene, which is approximately 4231 nucleotides in length, encodes a polypeptide which is approximately 1095 amino acid residues in length.

[0130] Various aspects of the invention are described in further detail in the following subsections:

[0131] I. Isolated Nucleic Acid Molecules

[0132] One aspect of the invention pertains to isolated nucleic acid molecules that encode 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides or biologically active portions thereof, as well as nucleic acid fragments sufficient for use as hybridization probes to identify 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-encoding nucleic acid molecules (e.g., 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA) and fragments for use as PCR primers for the amplification or mutation of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA) and RNA molecules (e.g., mRNA) and analogs of the DNA or RNA generated using nucleotide analogs. The nucleic acid molecule can be single-stranded or double-stranded, but preferably is double-stranded DNA.

[0133] The term “isolated nucleic acid molecule” includes nucleic acid molecules which are separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. For example, with regards to genomic DNA, the term “isolated” includes nucleic acid molecules which are separated from the chromosome with which the genomic DNA is naturally associated. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i. e., sequences located at the 5′ and 3′ ends of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell from which the nucleic acid is derived. Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized.

[0134] A nucleic acid molecule of the present invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ 3s ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______ or a portion thereof, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, as a hybridization probe, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989).

[0135] Moreover, a nucleic acid molecule encompassing all or a portion of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______ can be isolated by the polymerase chain reaction (PCR) using synthetic oligonucleotide primers designed based upon the sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______.

[0136] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.

[0137] In one embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in SEQ ID NO:1. The sequence of SEQ ID NO:1 corresponds to the human 8099 cDNA. This cDNA comprises sequences encoding the human 8099 polypeptide (i.e., “the coding region”, from nucleotides 180-2034) as well as 5′ untranslated sequences (nucleotides 1-179) and 3′ untranslated sequences (nucleotides 2035-2725). Alternatively, the nucleic acid molecule can comprise only the coding region of SEQ ID NO:1 (e.g., nucleotides 180-2034, corresponding to SEQ ID NO:3). Accordingly, in another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:3 and nucleotides 1-179 and 2035-2725 of SEQ ID NO:1. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:1 or SEQ ID NO:3.

[0138] In another embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in SEQ ID NO:4. The sequence of SEQ ID NO:4 corresponds to the human 46455 cDNA. This CDNA comprises sequences encoding the human 46455 polypeptide (i.e., “the coding region”, from nucleotides 376-1963) as well as 5′ untranslated sequences (nucleotides 1-375) and 3′ untranslated sequences (nucleotides 1964-2230). Alternatively, the nucleic acid molecule can comprise only the coding region of SEQ ID NO:4 (e.g., nucleotides 376-1963, corresponding to SEQ ID NO:6). Accordingly, in another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:6 and nucleotides 1-375 and 1964-2230 of SEQ ID NO:4. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:4 or SEQ ID NO:6.

[0139] In another embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in SEQ ID NO:7. This cDNA may comprise sequences encoding the human 54414 protein (e.g., the “coding region”, from nucleotides 225-3578), as well as 5′ untranslated sequence (nucleotides 1-224) and 3′ untranslated sequences (nucleotides 3579-4632) of SEQ ID NO:7. Alternatively, the nucleic acid molecule can comprise only the coding region of SEQ ID NO:7 (e.g., nucleotides 225-3578, corresponding to SEQ ID NO:9). Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention comprises SEQ ID NO:9 and nucleotides 1-224 of SEQ ID NO:7. In yet another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:9 and nucleotides 3579-4632 of SEQ ID NO:7. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:7 or SEQ ID NO:9.

[0140] In still another embodiment, the cDNA may comprise sequences encoding the human 53763 protein (e.g., the “coding region”, from nucleotides 561-2474), as well as 5′ untranslated sequence (nucleotides 1-560) and 3′ untranslated sequences (nucleotides 2475-2847) of SEQ ID NO:10. Alternatively, the nucleic acid molecule can comprise only the coding region of SEQ ID NO:10 (e.g., nucleotides 561-2474, corresponding to SEQ ID NO:6). Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention comprises SEQ ID NO:12 and nucleotides 1-560 of SEQ ID NO:10. In yet another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:12 and nucleotides 2475-2847 of SEQ ID NO:10. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:10 or SEQ ID NO:12.

[0141] In yet another embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in SEQ ID NO:13. The sequence of SEQ ID NO:13 corresponds to the human 67076 cDNA. This cDNA comprises sequences encoding the human 67076 polypeptide (i.e., “the coding region”, from nucleotides 524-3910) as well as 5′ untranslated sequences (nucleotides 1-523) and 3′ untranslated sequences (nucleotides 3911-6582). Alternatively, the nucleic acid molecule can comprise only the coding region of SEQ ID NO:13 (e.g., nucleotides 524-3910, corresponding to SEQ ID NO:15). Accordingly, in another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:15 and nucleotides 1-523 or 3911-6582 of SEQ ID NO:13. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:13 or SEQ ID NO:15.

[0142] In another embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in SEQ ID NO:16. The sequence of SEQ ID NO:16 corresponds to the human 67102 cDNA. This cDNA comprises sequences encoding the human 67102 polypeptide (i.e., “the coding region”, from nucleotides 274-4551) as well as 5′ untranslated sequences (nucleotides 1-273) and 3′ untranslated sequences (nucleotides 4552-6074). Alternatively, the nucleic acid molecule can comprise only the coding region of SEQ ID NO:16 (e.g., nucleotides 274-4551, corresponding to SEQ ID NO:18). Accordingly, in another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:18 and nucleotides 1- 273 or 4552-6074 of SEQ ID NO:16. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:16 or SEQ ID NO:18.

[0143] In still another embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in SEQ ID NO:19. The sequence of SEQ ID NO:19 corresponds to the human 44181 cDNA. This CDNA comprises sequences encoding the human 44181 polypeptide (i.e., “the coding region”, from nucleotides 167-3697) as well as 5′ untranslated sequences (nucleotides 1-166) and 3′ untranslated sequences (nucleotides 3698-7221). Alternatively, the nucleic acid molecule can comprise only the coding region of SEQ ID NO:19 (e.g., nucleotides 167-3697, corresponding to SEQ ID NO:21). Accordingly, in another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:21 and nucleotides 1-166 or 3698-7221 of SEQ ID NO:19. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:19 or SEQ ID NO:21.

[0144] In yet another embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in SEQ ID NO:22. The sequence of SEQ ID NO:22 corresponds to the human 67084FL cDNA. This cDNA comprises sequences encoding the human 67084FL polypeptide (i.e., “the coding region”, from nucleotides 156-3407) as well as 5′ untranslated sequences (nucleotides 1-155) and 3′ untranslated sequences (nucleotides 3408-4198). Alternatively, the nucleic acid molecule can comprise only-the coding region of SEQ ID NO:22 (e.g., nucleotides 156-3407, corresponding to SEQ ID NO:24). Accordingly, in another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:24 and nucleotides 1-155 or 3408-4198 of SEQ ID NO:22. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:22 or SEQ ID NO:24.

[0145] In a further embodiment, an isolated nucleic acid molecule of the invention comprises the nucleotide sequence shown in SEQ ID NO:25. The sequence of SEQ ID NO:25 corresponds to the human 67084alt cDNA. This cDNA comprises sequences encoding the human 67084alt polypeptide (i.e., “the coding region”, from nucleotides 156-3440) as well as 5′ untranslated sequences (nucleotides 1 -155) and 3′ untranslated sequences (nucleotides 3441-4231). Alternatively, the nucleic acid molecule can comprise only the coding region of SEQ ID NO:25 (e.g., nucleotides 156-3440, corresponding to SEQ ID NO:27). Accordingly, in another embodiment, the isolated nucleic acid molecule comprises SEQ ID NO:27 and nucleotides 1-155 or 3441-4231 of SEQ ID NO:25. In yet another embodiment, the nucleic acid molecule consists of the nucleotide sequence set forth as SEQ ID NO:25 or SEQ ID NO:27.

[0146] In still another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule which is a complement of the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, or a portion of any of these nucleotide sequences. A nucleic acid molecule which is complementary to the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, is one which is sufficiently complementary to the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, such that it can hybridize to the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, thereby forming a stable duplex.

[0147] In still another preferred embodiment, an isolated nucleic acid molecule of the present invention comprises a nucleotide sequence which is at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identical to the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27 (e.g., to the entire length of the nucleotide sequence), or to the nucleotide sequence (e.g., the entire length of the nucleotide sequence) of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, or a portion of any of these nucleotide sequences. In one embodiment, a nucleic acid molecule of the present invention comprises a nucleotide sequence which is at least (or no greater than) 50-100, 100-250, 250-500, 500-750, 750-1000, 1000-1250, 1250-1500, 1500-1750, 1750-2000, 2000-2250, 2250-2500, 2500-2750, 2750-3000, 3000-3250, 3250-3500, 3500-3750, 3750-4000, 4000-4250, 4250-4500, 4500-4750, 4750-5000, 5000-5250, 5250-5500, 5500-5750, 5750-6000, 6000-6250, 6250-6500, 6500-6750, 6750-7000, 7000-7250, 7250-7500 or more nucleotides in length and hybridizes under stringent hybridization conditions to a complement of a nucleic acid molecule of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______.

[0148] Moreover, the nucleic acid molecule of the invention can comprise only a portion of the nucleic acid sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, for example, a fragment which can be used as a probe or primer or a fragment encoding a portion of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, e.g., a biologically active portion of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. The nucleotide sequence determined from the cloning of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene allows for the generation of probes and primers designed for use in identifying and/or cloning other 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt family members, as well as 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt homologues from other species. The probe/primer typically comprises substantially purified oligonucleotide. The probe/primer (e.g., oligonucleotide) typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12 or 15, preferably about 20 or 25, more preferably about 30, 35, 40, 45, 50, 55, 60, 65, 75, 80, 85, 90, 95, or 100 or more consecutive nucleotides of a sense sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, of an anti-sense sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27 or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, or of a naturally occurring allelic variant or mutant of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______.

[0149] Exemplary probes or primers are at least 12, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 or more nucleotides in length and/or comprise consecutive nucleotides of an isolated nucleic acid molecule described herein. Probes based on the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences can be used to detect (e.g., specifically detect) transcripts or genomic sequences encoding the same or homologous polypeptides. In preferred embodiments, the probe further comprises a label group attached thereto, e.g., the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. In another embodiment a set of primers is provided, e.g., primers suitable for use in a PCR, which can be used to amplify a selected region of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence, e.g., a domain, region, site or other sequence described herein. The primers should be at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more nucleotides in length. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissue which misexpress a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, such as by measuring a level of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-encoding nucleic acid in a sample of cells from a subject e.g., detecting 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA levels or determining whether a genomic 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene has been mutated or deleted.

[0150] A nucleic acid fragment encoding a “biologically active portion of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide” can be prepared by isolating a portion of the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, which encodes a polypeptide having a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt biological activity (the biological activities of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides are described herein), expressing the encoded portion of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. In an exemplary embodiment, the nucleic acid molecule is at least 50-100, 100-250, 250-500, 500-750, 750-1000, 1000-1250, 1250-1500, 1500-1750, 1750-2000, 2000-2250, 2250-2500, 2500-2750, 2750-3000, 3000-3250, 3250-3500, 3500-3750, 3750-4000, 4000-4250, 4250-4500, 4500-4750, 4750-5000, 5000-5250, 5250-5500, 5500-5750, 5750-6000, 6000-6250, 6250-6500, 6500-6750, 6750-7000, 7000-7250, 7250-7500 or more nucleotides in length and encodes apolypeptide having a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity (as described herein).

[0151] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______. Such differences can be due to due to degeneracy of the genetic code, thus resulting in a nucleic acid which encodes the same 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides as those encoded by the nucleotide sequence shown in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, _____, _____, ______, or ______. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a polypeptide having an amino acid sequence which differs by at least 1, but no greater than 5, 10, 20, 50 or 100 amino acid residues from the amino acid sequence shown in SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, or the amino acid sequence encoded by the DNA insert of the plasmid deposited with the ATCC as Accession Number ______, ______, ______, ______, or ______. In yet another embodiment, the nucleic acid molecule encodes the amino acid sequence of human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. If an alignment is needed for this comparison, the sequences should be aligned for maximum homology.

[0152] Nucleic acid variants can be naturally occurring, such as allelic variants (same locus), homologues (different locus), and orthologues (different organism) or can be non naturally occurring. Non-naturally occurring variants can be made by mutagenesis techniques, including those applied to polynucleotides, cells, or organisms. The variants can contain nucleotide substitutions, deletions, inversions and insertions. Variation can occur in either or both the coding and non-coding regions. The variations can produce both conservative and non-conservative amino acid substitutions (as compared in the encoded product).

[0153] Allelic variants result, for example, from DNA sequence polymorphisms within a population (e.g., the human population) that lead to changes in the amino acid sequences of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides. Such genetic polymorphism in the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules which include an open reading frame encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, preferably a mammalian 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, and can further include non-coding regulatory sequences, and introns.

[0154] Accordingly, in one embodiment, the invention features isolated nucleic acid molecules which encode a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, or an amino acid sequence encoded by the DNA insert of the plasmid deposited with ATCC as Accession Number ______, _______, _______, _______, or ______, wherein the nucleic acid molecule hybridizes to a complement of a nucleic acid molecule comprising SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, for example, under stringent hybridization conditions.

[0155] Allelic variants of human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt include both functional and non-functional 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides.

[0156] Functional allelic variants are naturally occurring amino acid sequence variants of the human 8099 or 46455 polypeptides that have an 8099 or 46455 activity, e.g., maintain the ability to bind an 8099 or 46455 ligand or substrate and/or modulate sugar transport, or sugar homeostasis.

[0157] Functional allelic variants are naturally occurring amino acid sequence variants of the human 54414 or 53763 polypeptides that maintain the ability to, e.g., bind or interact with a 54414 or 53763 target molecule and/or modulate membrane excitability.

[0158] Functional allelic variants are naturally occurring amino acid sequence variants of the human 67076, 67102, 44181, 67084FL, or 67084alt polypeptides that have a 67076, 67102, 44181, 67084FL, or 67084alt activity, e.g., bind or interact with a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule, transport a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule across a cellular membrane, hydrolyze ATP, be phosphorylated or dephosphorylated, adopt an E1 conformation or an E2 conformation, and/or modulate cellular signaling, growth, proliferation, differentiation, absorption, or secretion.

[0159] Functional allelic variants will typically contain only conservative substitution of one or more amino acids of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, or substitution, deletion or insertion of non-critical residues in non-critical regions of the polypeptide.

[0160] Non-functional allelic variants are naturally occurring amino acid sequence variants of the human 8099 or 46455 polypeptides that do not have a 8099 or 46455 activity, e.g., maintain the ability to bind an 8099 or 46455 ligand or substrate and/or modulate sugar transport, or sugar homeostasis.

[0161] Non-functional allelic variants are naturally occurring amino acid sequence variants of the human 54414 or 53763 polypeptides that do not maintain the ability to, e.g., bind or interact with a 54414 or 53763 target molecule and/or modulate membrane excitability.

[0162] Non-functional allelic variants are naturally occurring amino acid sequence variants of the human 67076, 67102, 44181, 67084FL, or 67084alt polypeptides that do not have a 67076, 67102, 44181, 67084FL, or 67084alt activity, e.g., that do not have the ability to, e.g., bind or interact with a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule, transport a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule across a cellular membrane, hydrolyze ATP, be phosphorylated or dephosphorylated, adopt an E1 conforrnation or an E2 conformation, and/or modulate cellular signaling, growth, proliferation, differentiation, absorption, or secretion.

[0163] Non-functional allelic variants will typically contain a non-conservative substitution, a deletion, or insertion or premature truncation of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, or a substitution, insertion or deletion in critical residues or critical regions.

[0164] The present invention further provides non-human orthologues of the human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides. Orthologues of human 8099 or 46455 polypeptides are polypeptides that are isolated from non-human organisms and possess the same 8099 and/or 46455 activity, e.g., ligand binding and/or modulation of sugar transport mechanisms, as the human 8099 and/or 46455 polypeptide. Orthologues of the human 54414 or 53763 polypeptides are polypeptides that are isolated from non-human organisms and possess the same 54414 or 53763 target molecule binding mechanisms and/or ability to modulate membrane excitability of the human 54414 or 53763 polypeptides. Orthologues of human 67076, 67102, 44181, 67084FL, or 67084alt polypeptides are polypeptides that are isolated from non-human organisms and possess the same 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule binding mechanisms, phospholipid transporting activity, ATPase activity, and/or modulation of cellular signaling mechanisms of the human 67076, 67102, 44181, 67084FL, or 67084alt proteins as the human 67076, 67102, 44181, 67084FL, or 67084alt polypeptides.

[0165] Orthologues of the human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can readily be identified as comprising an amino acid sequence that is substantially identical to SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26.

[0166] Moreover, nucleic acid molecules encoding other 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt family members and, thus, which have a nucleotide sequence which differs from the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______ are intended to be within the scope of the invention. For example, another 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt cDNA can be identified based on the nucleotide sequence of human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. Moreover, nucleic acid molecules encoding 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides from different species, and which, thus, have a nucleotide sequence which differs from the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______ are intended to be within the scope of the invention. For example, amouse 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt cDNA can be identified based on the nucleotide sequence of a human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt.

[0167] Nucleic acid molecules corresponding to natural allelic variants and homologues of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt cDNAs of the invention can be isolated based on their homology to the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acids disclosed herein using the cDNAs disclosed herein, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions. Nucleic acid molecules corresponding to natural allelic variants and homologues of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt cDNAs of the invention can further be isolated by mapping to the same chromosome or locus as the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene.

[0168] Orthologues, homologues and allelic variants can be identified using methods known in the art (e.g., by hybridization to an isolated nucleic acid molecule of the present invention, for example, under stringent hybridization conditions). In one embodiment, an isolated nucleic acid molecule of the invention is at least 15, 20, 25, 30 or more nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______. In other embodiment, the nucleic acid is at least 50-100, 100-250, 250-500, 500-750, 750-1000, 1000-1250, 1250-1500, 1500-1750, 1750-2000, 2000-2250, 2250-2500, 2500-2750, 2750-3000, 3000-3250, 3250-3500, 3500-3750, 3750-4000, 4000-4250, 4250-4500, 4500-4750, 4750-5000, 5000-5250, 5250-5500, 5500-5750, 5750-6000, 6000-6250, 6250-6500, 6500-6750, 6750-7000, 7000-7250, 7250-7500 or more nucleotides in length.

[0169] As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences that are significantly identical or homologous to each other remain hybridized to each other. Preferably, the conditions are such that sequences at least about 70%, more preferably at least about 80%, even more preferably at least about 85% or 90% identical to each other remain hybridized to each other. Such stringent conditions are known to those skilled in the art and can be found in Current Protocols in Molecular Biology, Ausubel et al., eds., John Wiley & Sons, Inc. (1995), sections 2, 4 and 6. Additional stringent conditions can be found in Molecular Cloning: A Laboratory Manual, Sambrook et al., Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1989), chapters 7, 9 and 11. A preferred, non-limiting example of stringent hybridization conditions includes hybridization in 4× sodium chloride/sodium citrate (SSC), at about 65-70° C. (or hybridization in 4× SSC plus 50% formamide at about 42-50° C.) followed by one or more washes in 1× SSC, at about 65-70° C. A preferred, non-limiting example of highly stringent hybridization conditions includes hybridization in 1× SSC, at about 65-70° C. (or hybridization in 1× SSC plus 50% formamide at about 42-50° C.) followed by one or more washes in 0.3× SSC, at about 65-70° C. A preferred, non-limiting example of reduced stringency hybridization conditions includes hybridization in 4× SSC, at about 50-60° C. (or alternatively hybridization in 6× SSC plus 50% formamide at about 40-45° C.) followed by one or more washes in 2× SSC, at about 50-60° C. Ranges intermediate to the above-recited values, e.g., at 65-70° C. or at 42-50° C. are also intended to be encompassed by the present invention. SSPE (1× SSPE is 0.15M NaCl, 10 mM NaH₂PO₄, and 1.25mM EDTA, pH 7.4) can be substituted for SSC (1× SSC is 0.15M NaCl and 15mM sodium citrate) in the hybridization and wash buffers; washes are performed for 15 minutes each after hybridization is complete. The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10° C. less than the melting temperature (T_(m)) of the hybrid, where T_(m) is determined according to the following equations. For hybrids less than 18 base pairs in length, T_(m)(° C.)=2(# of A+T bases)+4(# of G+C bases). For hybrids between 18 and 49 base pairs in length, T_(m)(° C.)=81.5+16.6(log₁₀[Na²⁺])+0.41(% G+C)−(600/N), where N is the number of bases in the hybrid, and [Na⁺] is the concentration of sodium ions in the hybridization buffer ([Na²⁺] for 1× SSC=0.165 M). It will also be recognized by the skilled practitioner that additional reagents may be added to hybridization and/or wash buffers to decrease non-specific hybridization of nucleic acid molecules to membranes, for example, nitrocellulose or nylon membranes, including but not limited to blocking agents (e.g., BSA or salmon or herring sperm carrier DNA), detergents (e.g., SDS), chelating agents (e.g., EDTA), Ficoll, PVP and the like. When using nylon membranes, in particular, an additional preferred, non-limiting example of stringent hybridization conditions is hybridization in 0.25-0.5M NaH₂PO₄, 7% SDS at about 65° C., followed by one or more washes at 0.02M NaH₂PO₄, 1% SDS at 65° C., see e.g., Church and Gilbert (1984) Proc. Natl. Acad. Sci. USA 81:1991-1995, (or alternatively 0.2× SSC, 1% SDS).

[0170] Preferably, an isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to the sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, and corresponds to a naturally-occurring nucleic acid

[0171] molecule. As used herein, a “naturally-occurring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural polypeptide).

[0172] In addition to naturally-occurring allelic variants of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, thereby leading to changes in the amino acid sequence of the encoded 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, without altering the functional ability of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or _______. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt (e.g., the sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26) without altering the biological activity, whereas an “essential” amino acid residue is required for biological activity.

[0173] For example, amino acid residues that are conserved among the 8099 or 46455 polypeptides of the present invention, e.g., those present in a transmembrane domain and/or a sugar transporter family domain, are predicted to be particularly unamenable to alteration. Furthermore, additional amino acid residues that are conserved between the 8099 or 46455 polypeptides of the present invention and other members of the 8099 or 46455 family are not likely to be amenable to alteration.

[0174] Amino acid residues that are conserved among the 54414 or 53763 polypeptides of the present invention, e.g., those present in a P-loop or a pore domain, are predicted to be particularly unamenable to alteration. Furthermore, additional amino acid residues that are conserved between the 54414 or 53763 polypeptides of the present invention and other members of the potassium channel family are not likely to be amenable to alteration.

[0175] Amino acid residues that are conserved among the 67076, 67102, 44181, 67084FL, or 67084alt polypeptides of the present invention, e.g., those present in a E1-E2 ATPases phosphorylation site, are predicted to be particularly unamenable to alteration. Furthermore, additional amino acid residues that are conserved between the 67076, 67102, 44181, 67084FL, or 67084alt polypeptides of the present invention and other members of the phospholipid transporter family are not likely to be amenable to alteration.

[0176] Accordingly, another aspect of the invention pertains to nucleic acid molecules encoding 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides that contain changes in amino acid residues that are not essential for activity. Such 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides differ in amino acid sequence from SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a polypeptide, wherein the polypeptide comprises an amino acid sequence at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26 (e.g., to the entire length of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26).

[0177] An isolated nucleic acid molecule encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide identical to the polypeptide of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded polypeptide. Mutations can be introduced into SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______ by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutarnic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted nonessential amino acid residue in a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide is preferably replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt biological activity to identify mutants that retain activity. Following mutagenesis of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, ______, _______, ______, ______, or ______, the encoded polypeptide can be expressed recombinantly and the activity of the polypeptide can be determined.

[0178] In a preferred embodiment, a mutant 8099 and/or 46455 polypeptide can be assayed for the ability to (1) bind a monosaccharide, e.g., D-glucose, D-fructose, D-galactose, and/or mannose, (2) transport monosaccharides across a cell membrane, (3) influence insulin and/or glucagon secretion, (4) maintain sugar homeostasis in a cell, (5) function as a neuronal transporter, and (6) mediate trans-epithelial movement in a cell.

[0179] In another preferred embodiment, a mutant 54414 and/or 53763 protein can be assayed for the ability to (i) interact with a 54414 and/or 53763 substrate (e.g., a potassium ion or a cyclic nucleotide); (ii) conduct or transport a 54414 and/or 53763 substrate across a cellular membrane; (iii) interact with a second non-54414 and/or 53763 protein (e.g., a 54414 and/or 53763 polypeptide or a 54414 and/or 53763 -potassium channel subunit); (iv) modulate (e.g., maintain and/or rectify) membrane potentials; (v) regulate target molecule availability or activity; (vi) modulate intra- or intercellular signaling and/or gene transcription (e.g., either directly or indirectly); (viii) generate outwardly rectifying currents; (viii) modulate membrane excitability; (ix) modulate the release of neurotransmitters; (x) regulate contractility (e.g., of smooth muscle cells), secretion, and/or synaptic transmission; and/or (xi) modulate processes which underlie learning and memory.

[0180] In a further preferred embodiment, a mutant 54414 protein can be assayed for the ability to (i) interact with maxi-K potassium channels (i.e., large conductance channels, in particular Slo); (ii) modulate maxi-K potassium channel activity (e.g., Slo-mediated activities); (iii) generate intermediate conductance channels; and/or (iv) regulate contractility (e.g., of smooth muscle cells), secretion, and/or synaptic transmission, in particular, via modulation of Slo.

[0181] In still a further preferred embodiment, a mutant 53763 protein can be assayed for the ability to (i) interact with Shaker (Sh) potassium channels and/or channel subunits; (ii) modulate Shaker (Sh) potassium channel activity (e.g., termination of prolonged membrane depolarization); and/or (iii) modulation of high voltage activating channel activity and/or inactivating channel activity, and the like.

[0182] In yet another preferred embodiment, a mutant 67076, 67102, 44181, 67084FL, and/or 67084alt polypeptide can be assayed for the ability to (i) interact with a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., a phospholipid, ATP, or a non-67076, 67102, 44181, 67084FL, or 67084alt protein); (ii) transport a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., an aminophospholipid such as phosphatidylserine or phosphatidylethanolamine) from one side of a cellular membrane to the other; (iii) be phosphorylated or dephosphorylated; (iv) adopt an E1 conformation or an E2 conformation; (v) convert a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule to a product (e.g., hydrolysis of ATP); (vi) interact with a second non-67076, 67102, 44181, 67084FL, or 67084alt protein; (vii) modulate substrate or target molecule location (e.g., modulation of phospholipid location within a cell and/or location with respect to a cellular membrane); (viii) maintain aminophospholipid gradients; (ix) modulate intra- or intercellular signaling and/or gene transcription (e.g., either directly or indirectly); and/or (x) modulate cellular proliferation, growth, differentiation, apoptosis, absorption, or secretion.

[0183] In addition to the nucleic acid molecules encoding 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides described above, another aspect of the invention pertains to isolated nucleic acid molecules which are antisense thereto. In an exemplary embodiment, the invention provides an isolated nucleic acid molecule which is antisense to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule (e.g., is antisense to the coding strand of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule). An “antisense” nucleic acid comprises a nucleotide sequence which is complementary to a “sense” nucleic acid encoding a polypeptide, e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence. Accordingly, an antisense nucleic acid can hydrogen bond to a sense nucleic acid. The antisense nucleic acid can be complementary to an entire 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt coding strand, or to only a portion thereof. In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues (e.g., the coding region of human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt corresponds to SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:12, and SEQ ID NO:15, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:24, and SEQ ID NO:27, respectively). In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (i. e., also referred to as 5′ and 3′ untranslated regions).

[0184] Given the coding strand sequences encoding 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt disclosed herein (e.g., SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:12, and SEQ ID NO:15, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:24, and SEQ ID NO:27), antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA, but more preferably is an oligonucleotide which is antisense to only a portion of the coding or noncoding region of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA (e.g., between the −10 and +10 regions of the start site of a gene nucleotide sequence). An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis and enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids, e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used. Examples of modified nucleotides which can be used to generate the antisense nucleic acid include 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i. e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).

[0185] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to thereby inhibit expression of the polypeptide, e.g., by inhibiting transcription and/or translation. The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule which binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention include direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface, e.g., by linking the antisense nucleic acid molecules to peptides or antibodies which bind to cell surface receptors or antigens. The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient intra-cellular concentrations of the antisense molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.

[0186] In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other (Gaultier et al (1987) Nucleic Acids. Res. 15:6625-6641). The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (Inoue et al. (1987) Nucleic Acids Res. 15:6131-6148) or a chimeric RNA-DNA analogue (Inoue et al. (1987) FEBS Lett. 215:327-330).

[0187] In still another embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity which are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes (described in Haselhoff and Gerlach (1988) Nature 334:585-591)) can be used to catalytically cleave 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA transcripts to thereby inhibit translation of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA. A ribozyme having specificity for a 8099-, 46455-, 54414-, 53763-, 67076-, 67102-, 44181-, 67084FL-, or 67084alt-encoding nucleic acid can be designed based upon the nucleotide sequence of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt CDNA disclosed herein (i.e., SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the nucleotide sequence of the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a 8099-, 46455-, 54414-, 53763-, 67076-, 67102-, 44181-, 67084FL-, or 67084alt-encoding mRNA. See, e.g., Cech et al. U.S. Pat. No. 4,987,071; and Cech et al. U.S. Patent No. 5,116,742. Alternatively, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA can be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel, D. and Szostak, J. W. (1993) Science 261:1411-1418.

[0188] Alternatively, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt (e.g., the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt promoter and/or enhancers) to form triple helical structures that prevent transcription of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene in target cells. See generally, Helene, C. (1991) Anticancer Drug Des. 6(6):569-84; Helene, C. et al. (1992) Ann. N. Y. Acad. Sci. 660:27-36; and Maher, L. J. (1992) Bioassays 14(12):807-15.

[0189] In yet another embodiment, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules of the present invention can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acid molecules can be modified to generate peptide nucleic acids (see Hyrup B. et al. (1996) Bioorganic & Medicinal Chemistry 4 (1): 5-23). As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics, e.g., DNA mimics, in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleobases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomers can be performed using standard solid phase peptide synthesis protocols as described in Hyrup B. et al. (1996) supra; Perry-O'Keefe et al. Proc. Natl. Acad. Sci. 93: 14670-675.

[0190] PNAs of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, for example, inducing transcription or translation arrest or inhibiting replication. PNAs of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules can also be used in the analysis of single base pair mutations in a gene, (e.g., by PNA-directed PCR clamping); as ‘artificial restriction enzymes’ when used in combination with other enzymes, (e.g., S1 nucleases (Hyrup B. (1996) supra)); or as probes or primers for DNA sequencing or hybridization (Hyrup B. et al. (1996) supra; Perry-O'Keefe supra).

[0191] In another embodiment, PNAs of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be modified, (e.g., to enhance their stability or cellular uptake), by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules can be generated which may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes, (e.g., RNase H and DNA polymerases), to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleobases, and orientation (Hyrup B. (1996) supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup B. (1996) supra and Finn P. J. et al. (1996) Nucleic Acids Res. 24 (17): 3357-63. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry and modified nucleoside analogs, e.g., 5′-(4-methoxytrityl) amino-5′-deoxy-thymidine phosphoramidite, can be used as a between the PNA and the 5′ end of DNA (Mag, M. et al. (1989) Nucleic Acid Res. 17: 5973-88). PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment (Finn P. J. et al. (1996) supra). Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment (Peterser, K. H. et al. (1975) Bioorganic Med. Chem. Lett. 5: 1119-11124).

[0192] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger et al. (1989) Proc. Natl. Acad Sci. USA 86:6553-6556; Lemaitre et al. (1987) Proc. Natl. Acad. Sci. USA 84:648-652; PCT Publication No. W088/09810) or the blood-brain barrier (see, e.g., PCT Publication No. W089/10134). In addition, oligonucleotides can be modified with hybridization-triggered cleavage agents (See, e.g., Krol et al. (1988) Bio-Techniques 6:958-976) or intercalating agents. (See, e.g., Zon (1988) Pharm. Res. 5:539-549). To this end, the oligonucleotide may be conjugated to another molecule, (e.g., a peptide, hybridization triggered cross-linking agent, transport agent, or hybridization-triggered cleavage agent).

[0193] Alternatively, the expression characteristics of an endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene within a cell line or microorganism may be modified by inserting a heterologous DNA regulatory element into the genome of a stable cell line or cloned microorganism such that the inserted regulatory element is operatively linked with the endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene. For example, an endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene which is normally “transcriptionally silent”, i.e., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene which is normally not expressed, or is expressed only at very low levels in a cell line or microorganism, may be activated by inserting a regulatory element which is capable of promoting the expression of a normally expressed gene product in that cell line or microorganism. Alternatively, a transcriptionally silent, endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene may be activated by insertion of a promiscuous regulatory element that works across cell types.

[0194] A heterologous regulatory element may be inserted into a stable cell line or cloned microorganism, such that it is operatively linked with an endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, using techniques, such as targeted homologous recombination, which are well known to those of skill in the art, and described, e.g., in Chappel, U.S. Pat. No. 5,272,071; PCT publication No. WO 91/06667, published May 16, 1991.

[0195] II. Isolated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt Polypeptides and Anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt Antibodies

[0196] One aspect of the invention pertains to isolated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt or recombinant polypeptides and polypeptides, and biologically active portions thereof, as well as polypeptide fragments suitable for use as immunogens to raise anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies. In one embodiment, native 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides are produced by recombinant DNA techniques. Alternative to recombinant expression, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or polypeptide can be synthesized chemically using standard peptide synthesis techniques.

[0197] An “isolated” or “purified” polypeptide or biologically active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language “substantially free of cellular material” includes preparations of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide in which the polypeptide is separated from cellular components of the cells from which it is isolated or recombinantly produced. In one embodiment, the language “substantially free of cellular material” includes preparations of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide having less than about 30% (by dry weight) of non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide (also referred to herein as a “contaminating protein”), more preferably less than about 20% of non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, still more preferably less than about 10% of non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, and most preferably less than about 5% non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. When the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or biologically active portion thereof is recombinantly produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the protein preparation.

[0198] The language “substantially free of chemical precursors or other chemicals” includes preparations of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide in which the polypeptide is separated from chemical precursors or other chemicals which are involved in the synthesis of the polypeptide. In one embodiment, the language “substantially free of chemical precursors or other chemicals” includes preparations of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide having less than about 30% (by dry weight) of chemical precursors or non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt chemicals, more preferably less than about 20% chemical precursors or non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt chemicals, still more preferably less than about 10% chemical precursors or non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt chemicals, and most preferably less than about 5% chemical precursors or non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt chemicals.

[0199] As used herein, a “biologically active portion” of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide includes a fragment of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide which participates in an interaction between a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecule and a non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecule (e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate). Biologically active portions of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide include peptides comprising amino acid sequences sufficiently identical to or derived from the amino acid sequence of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, e.g., the amino acid sequence shown in SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, which include less amino acids than the full length 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, and exhibit at least one activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide.

[0200] Typically, biologically active portions of a 8099 or 46455 polypeptide comprise a domain or motif with at least one activity of the 8099 or 46455 polypeptide, e.g., modulating sugar transport mechanisms. A biologically active portion of an 8099 polypeptide can be a polypeptide which is, for example, 25, 30, 35, 40, 45, 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 600 or more amino acids in length. A biologically active portion of an 46455 polypeptide can be a polypeptide which is, for example, 25, 30, 35, 40, 45, 50, 75, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525 or more amino acids in length. Biologically active portions of an 8099 and/or an 46455 polypeptide can be used as targets for developing agents which modulate an 8099 or 46455 mediated activity, e.g, a sugar transport mechanism.

[0201] In one embodiment, a biologically active portion of an 8099 or an 46455 polypeptide comprises at least one transmembrane domain. It is to be understood that a preferred biologically active portion of an 8099 or an 46455 polypeptide of the present invention comprises at least one or more of the following domains: a transmembrane domain and/or a sugar transporter family domain. Moreover, other biologically active portions, in which other regions of the polypeptide are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native 8099 or 46455 polypeptide.

[0202] Moreover, biologically active portions of a 54414 or 53763 polypeptide comprise a domain or motif with at least one activity of the 54414 or 53763 polypeptide, e.g., modulation of intra- or inter-cellular signaling and/or gene expression, and/or modulate membrane excitability. A biologically active portion of a 54414 or 53763 polypeptide can be a polypeptide which is, for example, 10, 25, 50, 75, 100, 125, 150 or more amino acids in length. Biologically active portions of a 54414 or 53763 polypeptide can be used as targets for developing agents which modulate a 54414 or 53763 mediated activity, e.g., modulation of intra- or inter-cellular signaling and/or gene expression, and/or modulate membrane excitability.

[0203] In one embodiment, a biologically active portion of a 54414 or 53763 polypeptide comprises at least one transmembrane domain and/or a pore domain. Moreover, other biologically active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native 54414 or 53763 polypeptide.

[0204] Biologically active portions of a 67076, 67102, 44181, 67084FL, or 67084alt polypeptide comprise a domain or motif with at least one activity of the 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, e.g., the ability to interact with a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., a phospholipid; ATP; a non-67076, 67102, 44181, 67084FL, or 67084alt protein; or another 67076, 67102, 44181, 67084FL, or 67084alt protein or subunit); the ability to transport a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., a phospholipid) from one side of a cellular membrane to the other; the ability to be phosphorylated or dephosphorylated; the ability to adopt an E1 conformation or an E2 conformation; the ability to convert a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule to a product (e.g., the ability to hydrolyze ATP); the ability to interact with a second non-67076, 67102, 44181, 67084FL, or 67084alt protein; the ability to modulate intra- or inter-cellular signaling and/or gene transcription (e.g., either directly or indirectly); the ability to modulate cellular growth, proliferation, differentiation, absorption, and/or secretion. A biologically active portion of a 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be a polypeptide which is, for example, 10, 25, 50, 75, 100, 125, 150, 175, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650,700,750,800,850, 900,950, 1000, 1050, 1100, 1150, 1200, 1250, 1300, 1350, 1400, 1450, 1500, 1550 or more amino acids in length. Biologically active portions of a 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be used as targets for developing agents which modulate a 67076, 67102, 44181, 67084FL, or 67084alt mediated activity, e.g., modulating transport of biological molecules across membranes.

[0205] In one embodiment, a biologically active portion of a 67076, 67102, 44181, 67084FL, or 67084alt polypeptide comprises at least one at least one or more of the following domains, sites, or motifs: a transmembrane domain, an N-terminal large extramembrane domain, a C-terminal large extramembrane domain, an E1-E2 ATPases phosphorylation site, a P-type ATPase sequence 1 motif, a P-type ATPase sequence 2 motif, a P-type ATPase sequence 3 motif, and/or one or more phospholipid transporter specific amino acid resides. Moreover, other biologically active portions, in which other regions of the polypeptide are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native 67076, 67102, 44181, 67084FL, or 67084alt polypeptide.

[0206] Another aspect of the invention features fragments of the polypeptide having the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, for example, for use as immunogens. In one embodiment, a fragment comprises at least 5 amino acids (e.g., contiguous or consecutive amino acids) of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, or an amino acid sequence encoded by the DNA insert of the plasmid deposited with the ATCC as Accession Number ______, ______, ______, ______, or ______. In another embodiment, a fragment comprises at least 10, 15, 20, 25, 30, 35, 40, 45, 50 or more amino acids (e.g., contiguous or consecutive amino acids) of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, or an amino acid sequence encoded by the DNA insert of the plasmid deposited with the ATCC as Accession Number ______, _______, _______, ______, or ______.

[0207] In a preferred embodiment, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide has an amino acid sequence shown in SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26. In other embodiments, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide is substantially identical to SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, and retains the functional activity of the polypeptide of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail in subsection I above. In another embodiment, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide is a polypeptide which comprises an amino acid sequence at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26.

[0208] In another embodiment, the invention features a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide which is encoded by a nucleic acid molecule consisting of a nucleotide sequence at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identical to a nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or a complement thereof. This invention further features a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide which is encoded by a nucleic acid molecule consisting of a nucleotide sequence which hybridizes under stringent hybridization conditions to a complement of a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or a complement thereof.

[0209] To determine the percent identity of two amino acid sequences or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-identical sequences can be disregarded for comparison purposes). In a preferred embodiment, the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, even more preferably at least 60%, and even more preferably at least 70%, 80%, or 90% of the length of the reference sequence (e.g., when aligning a second sequence to the 8099 amino acid sequence of SEQ ID NO:2 having 617 amino acid residues, at least 185, preferably at least 246, more preferably at least 308, more preferably at least 370, even more preferably at least 431, and even more preferably at least 493 or 555 or more amino acid residues are aligned. In another preferred embodiment, the sequences being aligned for comparison purposes are globally aligned and percent identity is determined over the entire length of the sequences aligned. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position (as used herein amino acid or nucleic acid “identity” is equivalent to amino acid or nucleic acid “homology”). The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences.

[0210] The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In a preferred embodiment, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch (J. Mol. Biol. (48):444-453 (1970)) algorithm which has been incorporated into the GAP program in the GCG software package (available at the Accelrys website), using either a Blosum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. In yet another preferred embodiment, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package, using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. A preferred, non-limiting example of parameters to be used in conjunction with the GAP program include a Blosum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.

[0211] In another embodiment, the percent identity between two amino acid or nucleotide sequences is determined using the algorithm of E. Meyers and W. Miller (Comput. Appl. Biosci., 4:11-17 (1988)) which has been incorporated into the ALIGN program (version 2.0 or version 2.0U), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4.

[0212] The nucleic acid and polypeptide sequences of the present invention can further be used as a “query sequence” to perform a search against public databases to, for example, identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score=100, wordlength=12 to obtain nucleotide sequences homologous to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules of the invention. BLAST protein searches can be performed with the XBLAST program, score=100, wordlength=3, and a Blosum62 matrix to obtain amino acid sequences homologous to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide molecules of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., (1997) Nucleic Acids Res. 25(17):3389-3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. See the National Center for Biotechnology website.

[0213] The invention also provides 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt chimeric or fusion proteins. As used herein, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt “chimeric protein” or “fusion protein” comprises a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide operatively linked to a non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. A “8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide whereas a “non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a polypeptide which is not substantially homologous to the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, respectively, e.g., a polypeptide which is different from the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide and which is derived from the same or a different organism. Within a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fusion protein the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can correspond to all or a portion of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. In a preferred embodiment, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fusion protein comprises at least one biologically active portion of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. In another preferred embodiment, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fusion protein comprises at least two biologically active portions of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. Within the fusion protein, the term “operatively linked” is intended to indicate that the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide and the non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide are fused in-frame to each other. The non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be fused to the N-terminus or C-terminus of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide.

[0214] For example, in one embodiment, the fusion protein is a GST-8099, -46455, -54414,-53763, -67076, -67102, -44181, -67084FL, or -67084alt fusion protein in which the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences are fused to the C-terminus of the GST sequences. Such fusion proteins can facilitate the purification of recombinant 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt.

[0215] In another embodiment, the fusion protein is a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and/or secretion of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be increased through the use of a heterologous signal sequence.

[0216] The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fusion proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject in vivo. The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fusion proteins can be used to affect the bioavailability of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate. Use of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fusion proteins may be useful therapeutically for the treatment of disorders caused by, for example, (i) aberrant modification or mutation of a gene encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide; (ii) mis-regulation of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene; and (iii) aberrant post-translational modification of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide.

[0217] Moreover, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-fusion proteins of the invention can be used as immunogens to produce anti-8099, anti-46455, anti-54414, anti-53763, anti-67076, anti-67102, anti-44181, anti-67084FL, and/or anti-67084alt antibodies in a subject, to purify 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt ligands and in screening assays to identify molecules which inhibit the interaction with or transport of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate.

[0218] Preferably, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt chimeric or fusion protein of the invention is produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, for example by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, for example, Current Protocols in Molecular Biology, eds. Ausubel et al. John Wiley & Sons: 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). A 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide.

[0219] The present invention also pertains to variants of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides which function as either 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt agonists (mimetics) or as 8099, 46455 , 54414 , 53763 , 67076 , 67102 , 44181 , 67084FL, or 67084alt antagonists. Variants of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can be generated by mutagenesis, e.g., discrete point mutation or truncation of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. An agonist of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can retain substantially the same, or a subset, of the biological activities of the naturally occurring form of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. An antagonist of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can inhibit one or more of the activities of the naturally occurring form of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide by, for example, competitively modulating a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-mediated activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the polypeptide has fewer side effects in a subject relative to treatment with the naturally occurring form of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide.

[0220] In one embodiment, variants of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide which function as either 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt agonists (mimetics) or as 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antagonists can be identified by screening combinatorial libraries of mutants, e.g., truncation mutants, of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide for 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide agonist or antagonist activity. In one embodiment, a variegated library of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences therein. There are a variety of methods which can be used to produce libraries of potential 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences. Methods for synthesizing degenerate oligonucleotides are known in the art (see, e.g., Narang, S. A. (1983) Tetrahedron 39:3; Itakura et al. (1984) Annu. Rev. Biochem. 53:323; Itakuraetal. (1984) Science 198:1056; Ike etal. (1983) Nucleic Acid Res. 11:477.

[0221] In addition, libraries of fragments of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide coding sequence can be used to generate a variegated population of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fragments for screening and subsequent selection of variants of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double stranded DNA which can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, an expression library can be derived which encodes N-terminal, C-terminal and internal fragments of various sizes of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide.

[0222] Several techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening eDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides. The most widely used techniques, which are amenable to high through-put analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique which enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt variants (Arkin and Yourvan (1992) Proc. Natl. Acad. Sci. USA 89:7811-7815; Delgrave et al. (1993) Protein Engineering 6(3):327-331).

[0223] In one embodiment, cell based assays can be exploited to analyze a variegated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt library. For example, a library of expression vectors can be transfected into a cell line, which ordinarily responds to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt in a particular 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate-dependent manner. The transfected cells are then contacted with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt and the effect of the expression of the mutant on signaling by the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate can be detected, e.g., phospholipid transport (e.g., by measuring phospholipid levels inside the cell or its various cellular compartments, within various cellular membranes, or in the extra-cellular medium), hydrolysis of ATP, phosphorylation or dephosphorylation of the HEAT protein, and/or gene transcription. Plasmid DNA can then be recovered from the cells which score for inhibition, or alternatively, potentiation of signaling by the HEAT substrate, or which score for increased or decreased levels of phospholipid transport or ATP hydrolysis, and the individual clones further characterized.

[0224] An isolated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that bind 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt using standard techniques for polyclonal and monoclonal antibody preparation. A full-length 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be used or, alternatively, the invention provides antigenic peptide fragments of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt for use as immunogens. The antigenic peptide of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt comprises at least 8 amino acid residues of the amino acid sequence shown in SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26 and encompasses an epitope of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt such that an antibody raised against the peptide forms a specific immune complex with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. Preferably, the antigenic peptide comprises at least 10 amino acid residues, more preferably at least 15 amino acid residues, even more preferably at least 20 amino acid residues, and most preferably at least 30 amino acid residues.

[0225] Preferred epitopes encompassed by the antigenic peptide are regions of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt that are located on the surface of the polypeptide, e.g., hydrophilic regions, as well as regions with high antigenicity (see, for example, FIGS. 2, 9, 13, 17, 21, 25, 29, 33, and 37).

[0226] A 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt immunogen typically is used to prepare antibodies by immunizing a suitable subject, (e.g., rabbit, goat, mouse or other mammal) with the immunogen. An appropriate immunogenic preparation can contain, for example, recombinantly expressed 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or a chemically synthesized 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. The preparation can further include an adjuvant, such as Freund's complete or incomplete adjuvant, or similar immunostimulatory agent. Immunization of a suitable subject with an immunogenic 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt preparation induces a polyclonal anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody response.

[0227] Accordingly, another aspect of the invention pertains to polyclonal anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies. The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain an antigen binding site which specifically binds (immunoreacts with) an antigen, such as 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. Examples of immunologically active portions of immunoglobulin molecules include F(ab) and F(ab′)₂ fragments which can be generated by treating the antibody with an enzyme such as pepsin. The invention provides polyclonal and monoclonal antibodies that bind 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. The term “monoclonal antibody” or “monoclonal antibody composition”, as used herein, refers to a population of antibody molecules that contain only one species of an antigen binding site capable of immunoreacting with a particular epitope of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. A monoclonal antibody composition thus typically displays a single binding affinity for a particular 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide with which it immunoreacts.

[0228] Polyclonal anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies can be prepared as described above by immunizing a suitable subject with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt immunogen. The anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody titer in the immunized subject can be monitored over time by standard techniques, such as with an enzyme linked immunosorbent assay (ELISA) using immobilized 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. If desired, the antibody molecules directed against 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as protein A chromatography to obtain the IgG fraction. At an appropriate time after immunization, e.g., when the anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody titers are highest, antibody-producing cells can be obtained from the subject and used to prepare monoclonal antibodies by standard techniques, such as the hybridoma technique originally described by Kohler and Milstein (1975) Nature 256:495-497) (see also, Brown et al. (1981) J. Immunol. 127:539-46; Brown et al. (1980) J. Biol. Chem. 255:4980-83; Yeh et al. (1976) Proc. Natl. Acad. Sci. USA 76:2927-31; and Yeh et al. (1982) Int. J. Cancer 29:269-75), the more recent human B cell hybridoma technique (Kozbor et al. (1983) Immunol Today 4:72), the EBV-hybridoma technique (Cole et al. (1985), Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96) or trioma techniques. The technology for producing monoclonal antibody hybridomas is well known (see generally R. H. Kenneth, in Monoclonal Antibodies: A New Dimension In Biological Analyses, Plenum Publishing Corp., New York, N.Y. (1980); E. A. Lemer (1981) Yale J. Biol. Med., 54:387-402; M. L. Gefter et al. (1977) Somatic Cell Genet. 3:231-36). Briefly, an immortal cell line (typically a myeloma) is fused to lymphocytes (typically splenocytes) from a mammal immunized with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt immunogen as described above, and the culture supernatants of the resulting hybridoma cells are screened to identify a hybridoma producing a monoclonal antibody that binds 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt.

[0229] Any of the many well known protocols used for fusing lymphocytes and immortalized cell lines can be applied for the purpose of generating an anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt monoclonal antibody (see, e.g., G. Galfre et al. (1977) Nature 266:55052; Gefter et al. Somatic Cell Genet., cited supra; Lerner, Yale J Biol. Med., cited supra; Kenneth, Monoclonal Antibodies, cited supra). Moreover, the ordinarily skilled worker will appreciate that there are many variations of such methods which also would be useful. Typically, the immortal cell line (e.g., a myeloma cell line) is derived from the same mammalian species as the lymphocytes. For example, murine hybridomas can be made by fusing lymphocytes from a mouse immunized with an immunogenic preparation of the present invention with an immortalized mouse cell line. Preferred immortal cell lines are mouse myeloma cell lines that are sensitive to culture medium containing hypoxanthine, aminopterin and thymidine (“HAT medium”). Any of a number of myeloma cell lines can be used as a fusion partner according to standard techniques, e.g., the P3-NS1/1-Ag4-1, P3-x63-Ag8.653 or Sp2/O-Ag14 myeloma lines. These myeloma lines are available from ATCC. Typically, HAT-sensitive mouse myeloma cells are fused to mouse splenocytes using polyethylene glycol (“PEG”). Hybridoma cells resulting from the fusion are then selected using HAT medium, which kills unfused and unproductively fused myeloma cells (unfused splenocytes die after several days because they are not transformed). Hybridoma cells producing a monoclonal antibody of the invention are detected by screening the hybridoma culture supernatants for antibodies that bind 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt, e.g., using a standard ELISA assay.

[0230] Alternative to preparing monoclonal antibody-secreting hybridomas, a monoclonal anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt to thereby isolate immunoglobulin library members that bind 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. Kits for generating and screening phage display libraries are commercially available (e.g., the Pharmacia Recombinant Phage Antibody System, Catalog No. 27-9400-01; and the Stratagene SurfZAP™ Phage Display Kit, Catalog No. 240612). Additionally, examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, Ladner et al. U.S. Pat. No. 5,223,409; Kang et al. PCT International Publication No. WO 92/18619; Dower et al. PCT International Publication No. WO 91/17271; Winter et al. PCT International Publication WO 92/20791; Markland et al. PCT International Publication No. WO 92/15679; Breitling et al. PCT International Publication WO 93/01288; McCafferty et al. PCT International Publication No. WO 92/01047; Garrard et al. PCT International Publication No. WO 92/09690; Ladner et al. PCT International Publication No. WO 90/02809; Fuchs et al. (1991) Bio/Technology 9:1370-1372; Hay et al. (1992) Hum. Antibod. Hybridomas 3:81-85; Huse et al. (1989) Science 246:1275-1281; Griffiths et al. (1993) EMBO J. 12:725-734; Hawkins et al. (1992) J. Mol. Biol. 226:889-896; Clarkson et al. (1991) Nature 352:624-628; Gram et al. (1992) Proc. Natl. Acad. Sci. USA 89:3576-3580; Garrad etal. (1991) Bio/Technology 9:1373-1377; Hoogenboom et al. (1991) Nuc. Acid Res. 19:4133-4137; Barbas et al. (1991) Proc. Natl. Acad. Sci. USA 88:7978-7982; and McCafferty et al. Nature (1990) 348:552-554.

[0231] Additionally, recombinant anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies, such as chimeric and humanized monoclonal antibodies, comprising both human and non-human portions, which can be made using standard recombinant DNA techniques, are within the scope of the invention. Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art, for example using methods described in Robinson et al. International Application No. PCT/US86/02269; Akira, et al. European Patent Application 184,187; Taniguchi, M., European Patent Application 171,496; Morrison et al. European Patent Application 173,494; Neuberger et al. PCT International Publication No. WO 86/01533; Cabilly et al. U.S. Pat. No. 4,816,567; Cabilly et al. European Patent Application 125,023; Better et al. (1988) Science 240:1041-1043; Liu et al. (1987) Proc. Natl. Acad. Sci. USA 84:3439-3443; Liu et al. (1987) J. Immunol. 139:3521-3526; Sun et al. (1987) Proc. Natl. Acad. Sci. USA 84:214-218; Nishimura et al. (1987) Canc. Res. 47:999-1005; Wood et al. (1985) Nature 314:446-449; and Shaw et al. (1988) J. Natl. Cancer Inst. 80:1553-1559); Morrison, S. L. (1985) Science 229:1202-1207; Oi et al. (1986) BioTechniques 4:214; Winter U.S. Pat. No. 5,225,539; Jones et al. (1986) Nature 321:552-525; Verhoeyan et al. (1988) Science 239:1534; and Beidler et al. (1988) J. Immunol. 141:4053-4060.

[0232] An anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody (e.g., monoclonal antibody) can be used to isolate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt by standard techniques, such as affinity chromatography or immunoprecipitation. An anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody can facilitate the purification of natural 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt from cells and of recombinantly produced 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expressed in host cells. Moreover, an anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody can be used to detect 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. Anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies can be used diagnostically to monitor polypeptide levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ¹²⁵I, ¹³¹I, ³⁵S or ³H.

[0233] III. Recombinant Expression Vectors and Host Cells

[0234] Another aspect of the invention pertains to vectors, for example recombinant expression vectors, containing a nucleic acid containing a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule or vectors containing a nucleic acid molecule which encodes a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide (or a portion thereof). As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as “expression vectors”. In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.

[0235] The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, which is operatively linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner which allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell). The term “regulatory sequence” is intended to include promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel; Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those which direct constitutive expression of a nucleotide sequence in many types of host cells and those which direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of polypeptide desired, and the like. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, mutant forms of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, fusion proteins, and the like).

[0236] Accordingly, an exemplary embodiment provides a method for producing a polypeptide, preferably a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, by culturing in a suitable medium a host cell of the invention (e.g., a mammalian host cell such as a non-human mammalian cell) containing a recombinant expression vector, such that the polypeptide is produced.

[0237] The recombinant expression vectors of the invention can be designed for expression of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides in prokaryotic or eukaryotic cells. For example, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can be expressed in bacterial cells such as E. coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

[0238] Expression of proteins in prokaryotes is most often carried out in E. coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: 1) to increase expression of recombinant protein; 2) to increase the solubility of the recombinant protein; and 3) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith, D. B. and Johnson, K. S. (1988) Gene 67:31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) which fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.

[0239] Purified fusion proteins can be utilized in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity assays, (e.g., direct assays or competitive assays described in detail below), or to generate antibodies specific for 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, for example. In a preferred embodiment, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fusion protein expressed in a retroviral expression vector of the present invention can be utilized to infect bone marrow cells which are subsequently transplanted into irradiated recipients. The pathology of the subject recipient is then examined after sufficient time has passed (e.g., six (6) weeks).

[0240] Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amann etal., (1988) Gene 69:301-315) and pET lid (Studier et al., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 60-89). Target gene expression from the pTrc vector relies on host RNA polymerase transcription from a hybrid trp-lac fusion promoter. Target gene expression from the pET 1 d vector relies on transcription from a T7 gn10-lac fusion promoter mediated by a coexpressed viral RNA polymerase (T7 gn1). This viral polymerase is supplied by host strains BL21(DE3) or HMS174(DE3) from a resident prophage harboring a T7 gn1 gene under the transcriptional control of the lacUV 5 promoter.

[0241] One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein (Gottesman, S., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 119-128). Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in E. coli (Wada et al., (1992) Nucleic Acids Res. 20:2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.

[0242] In another embodiment, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression vector is a yeast expression vector. Examples of vectors for expression in yeast S. cerevisiae include pYepSec1 (Baldari, et al., (1987) Embo J. 6:229-234), pMFa (Kurjan and Herskowitz, (1982) Cell 30:933-943), pJRY88 (Schultz et al., (1987) Gene 54:113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

[0243] Alternatively, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., Sf 9 cells) include the pAc series (Smith et al. (1983) Mol. Cell Biol. 3:2156-2165) and the pVL series (Lucklow and Summers (1989) Virology 170:31-39).

[0244] In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, B. (1987) Nature 329:840) and pMT2PC (Kaufman et al. (1987) EMBO J. 6:187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, Adenovirus 2, cytomegalovirus and Simian Virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see chapters 16 and 17 of Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.

[0245] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert et al. (1987) Genes Dev. 1:268-277), lymphoid-specific promoters (Calame and Eaton (1988) Adv. Immunol. 43:235-275), in particular promoters of T cell receptors (Winoto and Baltimore (1989) EMBO J. 8:729-733) and immunoglobulins (Banerji et al. (1983) Cell 33:729-740; Queen and Baltimore (1983) Cell 33:741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle (1989) Proc. Natl. Acad. Sci. USA 86:5473-5477), pancreas-specific promoters (Edlund et al. (1985) Science 230:912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, for example the murine hox promoters (Kessel and Gruss (1990) Science 249:374-379) and the α-fetoprotein promoter (Campes and Tilghman (1989) Genes Dev. 3:537-546).

[0246] The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively linked to a regulatory sequence in a manner which allows for expression (by transcription of the DNA molecule) of an RNA molecule which is antisense to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen which direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen which direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see Weintraub, H. et al., Antisense RNA as a molecular tool for genetic analysis, Reviews—Trends in Genetics, Vol. 1(1) 1986.

[0247] Another aspect of the invention pertains to host cells into which a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule of the invention is introduced, e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule within a vector (e.g., a recombinant expression vector) or a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule containing sequences which allow it to homologously recombine into a specific site of the host cell's genome. The terms “host cell” and “recombinant host cell” are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.

[0248] A host cell can be any prokaryotic or eukaryotic cell. For example, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.

[0249] Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms “transformation” and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.

[0250] For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Preferred selectable markers include those which confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection (e.g., cells that have incorporated the selectable marker gene will survive, while the other cells die).

[0251] A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide. Accordingly, the invention further provides methods for producing a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of the invention (into which a recombinant expression vector encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide has been introduced) in a suitable medium such that a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide is produced. In another embodiment, the method further comprises isolating a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide from the medium or the host cell.

[0252] The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences have been introduced into their genome or homologous recombinant animals in which endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences have been altered. Such animals are useful for studying the function and/or activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt and for identifying and/or evaluating modulators of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity. As used herein, a “transgenic animal” is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, and the like. A transgene is exogenous DNA which is integrated into the genome of a cell from which a transgenic animal develops and which remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a “homologous recombinant animal” is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.

[0253] A transgenic animal of the invention can be created by introducing a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-encoding nucleic acid into the male pronuclei of a fertilized oocyte, e.g., by microinjection, retroviral infection, and allowing the oocyte to develop in a pseudopregnant female foster animal. The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt cDNA sequence of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, or SEQ ID NO:13 can be introduced as a transgene into the genome of a non-human animal. Alternatively, a nonhuman homologue of a human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, such as a mouse or rat 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, can be used as a transgene. Alternatively, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene homologue, such as another 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt family member, can be isolated based on hybridization to the 8099, 46455, 54414, 53763, 67076, 67102,44181, 67084FL, or 67084alt cDNA sequences of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, ______, or ______ (described further in subsection I above) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably linked to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt transgene to direct expression of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866 and 4,870,009, both by Leder et al., U.S. Pat. No. 4,873,191 by Wagner et al. and in Hogan, B., Manipulating the Mouse Embryo, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986). Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt transgene in its genome and/or expression of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can further be bred to other transgenic animals carrying other transgenes.

[0254] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene. The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene can be a human gene (e.g., the cDNA of SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:12, or SEQ ID NO:15), but more preferably, is a non-human homologue of a human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene (e.g., a cDNA isolated by stringent hybridization with the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, or SEQ ID NO:13). For example, a mouse 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene can be used to construct a homologous recombination nucleic acid molecule, e.g., a vector, suitable for altering an endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene in the mouse genome. In a preferred embodiment, the homologous recombination nucleic acid molecule is designed such that, upon homologous recombination, the endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene is functionally disrupted (i.e., no longer encodes a functional protein; also referred to as a “knock out” vector). Alternatively, the homologous recombination nucleic acid molecule can be designed such that, upon homologous recombination, the endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene is mutated or otherwise altered but still encodes functional polypeptide (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide). In the homologous recombination nucleic acid molecule, the altered portion of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene is flanked at its 5′ and 3′ ends by additional nucleic acid sequence of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene to allow for homologous recombination to occur between the exogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene carried by the homologous recombination nucleic acid molecule and an endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene in a cell, e.g., an embryonic stem cell. The additional flanking 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid sequence is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5′ and 3′ ends) are included in the homologous recombination nucleic acid molecule (see, e.g., Thomas, K. R. and Capecchi, M. R. (1987) Cell 51:503 for a description of homologous recombination vectors). The homologous recombination nucleic acid molecule is introduced into a cell, e.g., an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene has homologously recombined with the endogenous 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene are selected (see e.g., Li, E. et al. (1992) Cell 69:915). The selected cells can then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras (see e.g., Bradley, A. in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987) pp. 113-152). A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination nucleic acid molecules, e.g., vectors, or homologous recombinant animals are described further in Bradley, A. (1991) Current Opinion in Biotechnology 2:823-829 and in PCT International Publication Nos.: WO 90/11354 by Le Mouellec et al.; WO 91/01140 by Smithies et al.; WO 92/0968 by Zijlstra et al.; and WO 93/04169 by Berns et al.

[0255] In another embodiment, transgenic non-human animals can be produced which contain selected systems which allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, see, e.g., Lakso et al. (1992) Proc. Natl. Acad. Sci. USA 89:6232-6236. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae (O'Gorman et al. (1991) Science 251:1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of “double” transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.

[0256] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, I. et a. (1997) Nature 385:810-813 and PCT International Publication Nos. WO 97/07668 and WO 97/07669. In brief, a cell, e.g., a somatic cell, from the transgenic animal can be isolated and induced to exit the growth cycle and enter G_(O) phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell, e.g., the somatic cell, is isolated.

[0257] IV. Pharmaceutical Compositions

[0258] The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules, fragments of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies, and or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt modulators, (also referred to herein as “active compounds”) of the invention can be incorporated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the nucleic acid molecule, polypeptide, or antibody and a pharmaceutically acceptable carrier. As used herein the language “pharmaceutically acceptable carrier” is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.

[0259] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjusT_(m)ent of tonicity such as sodium chloride or dextrose. pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

[0260] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor ELT™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyetheylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifingal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0261] Sterile injectable solutions can be prepared by incorporating the active compound (e.g., a fragment of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or an anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze-drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0262] Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

[0263] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer.

[0264] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

[0265] The compounds can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.

[0266] In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.

[0267] It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.

[0268] Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. Compounds which exhibit large therapeutic indices are preferred. While compounds that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to uninfected cells and, thereby, reduce side effects.

[0269] The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.

[0270] As defined herein, a therapeutically effective amount of polypeptide (i. e., an effective dosage) ranges from about 0.001 to 30 mg/kg body weight, preferably about 0.01 to 25 mg/kg body weight, more preferably about 0.1 to 20 mg/kg body weight, and even more preferably about 1 to 10 mg/kg, 2 to 9 mg/kg, 3 to 8 mg/kg, 4 to 7 mg/kg, or 5 to 6 mg/kg body weight. The skilled artisan will appreciate that certain factors may influence the dosage required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of a polypeptide or antibody can include a single treatment or, preferably, can include a series of treatments.

[0271] In a preferred example, a subject is treated with antibody or polypeptide in the range of between about 0.1 to 20 mg/kg body weight, one time per week for between about I to 10 weeks, preferably between 2 to 8 weeks, more preferably between about 3 to 7 weeks, and even more preferably for about 4, 5, or 6 weeks. It will also be appreciated that the effective dosage of antibody or polypeptide used for treatment may increase or decrease over the course of a particular treatment. Changes in dosage may result and become apparent from the results of diagnostic assays as described herein.

[0272] The present invention encompasses agents which modulate expression or activity. An agent may, for example, be a small molecule. For example, such small molecules include, but are not limited to, peptides, peptidomimetics, amino acids, amino acid analogs, polynucleotides, polynucleotide analogs, nucleotides, nucleotide analogs, organic or inorganic compounds (i.e.,. including heteroorganic and organometallic compounds) having a molecular weight less than about 10,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 5,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 1,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 500 grams per mole, and salts, esters, and other pharmaceutically acceptable forms of such compounds. It is understood that appropriate doses of small molecule agents depends upon a number of factors within the ken of the ordinarily skilled physician, veterinarian, or researcher. The dose(s) of the small molecule will vary, for example, depending upon the identity, size, and condition of the subject or sample being treated, further depending upon the route by which the composition is to be administered, if applicable, and the effect which the practitioner desires the small molecule to have upon the nucleic acid or polypeptide of the invention.

[0273] Exemplary doses include milligram or microgram amounts of the small molecule per kilogram of subject or sample weight (e.g., about 1 microgram per kilogram to about 500 milligrams per kilogram, about 100 micrograms per kilogram to about 5 milligrams per kilogram, or about 1 microgram per kilogram to about 50 micrograms per kilogram. It is furthermore understood that appropriate doses of a small molecule depend upon the potency of the small molecule with respect to the expression or activity to be modulated. Such appropriate doses may be determined using the assays described herein. When one or more of these small molecules is to be administered to an animal (e.g., a human) in order to modulate expression or activity of a polypeptide or nucleic acid of the invention, a physician, veterinarian, or researcher may, for example, prescribe a relatively low dose at first, subsequently increasing the dose until an appropriate response is obtained. In addition, it is understood that the specific dose level for any particular animal subject will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, gender, and diet of the subject, the time of administration, the route of administration, the rate of excretion, any drug combination, and the degree of expression or activity to be modulated.

[0274] Further, an antibody (or fragment thereof) may be conjugated to a therapeutic moiety such as a cytotoxin, a therapeutic agent or a radioactive metal ion. A cytotoxin or cytotoxic agent includes any agent that is detrimental to cells. Examples include taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy antliracin dione, mitoxantrone, mithramycin, actinomycin D, 1 -dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologues thereof. Therapeutic agents include, but are not limited to, antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine), alkylating agents (e.g., mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin), anthracyclines (e.g., daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (e.g., dactinomycin (formerly actinomycin), bleomycin, mithramycin, and anthramycin (AMC)), and anti-mitotic agents (e.g., vincristine and vinblastine).

[0275] The conjugates of the invention can be used for modifying a given biological response, the drug moiety is not to be construed as limited to classical chemical therapeutic agents. For example, the drug moiety may be a protein or polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin; a protein such as tumor necrosis factor, alpha-interferon, beta-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator; or, biological response modifiers such as, for example, lymphokines, interleukin-1 (“IL-1”), interleukin-2 (“IL-2”), interleukin-6 (“IL-6”), granulocyte macrophage colony stimulating factor (“GM-CSF”), granulocyte colony stimulating factor (“G-CSF”), or other growth factors.

[0276] Techniques for conjugating such therapeutic moiety to antibodies are well known, see, e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy”, in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery”, in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review”, in Monoclonal Antibodies '84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); “Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy”, in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., “The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates”, Immunol. Rev., 62:119-58 (1982). Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Pat. No. 4,676,980.

[0277] The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see U.S. Patent 5,328,470) or by stereotactic injection (see e.g., Chen et al. (1994) Proc. Natl. Acad. Sci. USA 91:3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells which produce the gene delivery system.

[0278] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0279] V. Uses and Methods of the Invention

[0280] The nucleic acid molecules, proteins, protein homologues, antibodies, and modulators described herein can be used in one or more of the following methods: a) screening assays; b) predictive medicine (e.g., diagnostic assays, prognostic assays, monitoring clinical trials, and pharmacogenetics); and c) methods of treatment (e.g., therapeutic and prophylactic).

[0281] As described herein, an 8099 and/or 46455 polypeptide of the invention has one or more of the following activities: (1) bind a monosaccharide, e.g., D-glucose, D-fructose, D-galactose, and/or mannose, (2) transport monosaccharides across a cell membrane, (3) influence insulin and/or glucagon secretion, (4) maintain sugar homeostasis in a cell, (5) function as a neuronal transporter, and (6) mediate trans-epithelial movement in a cell.

[0282] As described herein, a 54414 and/or 53763 protein of the invention has one or more of the following activities: (i) interaction with a 54414 or 53763 substrate (e.g., a potassium ion or a cyclic nucleotide); (ii) conductance or transport of a 54414 or 53763 substrate across a cellular membrane; (iii) interaction with a second non-54414 or 53763 protein (e.g., a 54414 or 53763 polypeptide or a non-54414 or 53763 potassium channel subunit); (iv) modulation (e.g., maintenance and/or rectification) of membrane potentials; (v) regulation of target molecule availability or activity; (vi) modulation of intra- or intercellular signaling and/or gene transcription (e.g., either directly or indirectly); (viii) generation of outwardly rectifying currents; (viii) modulation of membrane excitability; (ix) modulation of the release of neurotransmitters; (x) regulation of contractility (e.g., of smooth muscle cells), secretion, and/or synaptic transmission; and/or (xi) modulation of processes which underlie learning and memory.

[0283] Preferred activities of 54414 further include at least one of the following activities: (i) interaction with maxi-K potassium channels (i.e., large conductance channels, in particular Slo); (ii) modulation of maxi-K potassium channel activity (e.g., Slo-mediated activities); (iii) generation of intermediate conductance channels; and/or (iv) regulation of contractility (e.g., of smooth muscle cells), secretion, and/or synaptic transmission, in particular, via modulation of Slo.

[0284] Preferred activities of 53763 further include at least one of the following activities: (i) interaction with Shaker (Sh) potassium channels and/or channel subunits; (ii) modulation of Shaker (Sh) potassium channel activity (e.g., termination of prolonged membrane depolarization; (iii) modulation of high voltage activating channel activity and/or inactivating channel activity, and the like.

[0285] As described herein, a 67076, 67102, 44181, 67084FL, or 67084alt polypeptide of the invention has one or more of the following activities: (i) interaction with a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., a phospholipid, ATP, or a non-67076, 67102, 44181, 67084FL, or 67084alt protein); (ii) transport of a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., an aminophospholipid such as phosphatidylserine or phosphatidylethanolamine) from one side of a cellular membrane to the other; (iii) the ability to be phosphorylated or dephosphorylated; (iv) adoption of an E1 conformation or an E2 conformation; (v) conversion of a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule to a product (e.g., hydrolysis of ATP); (vi) interaction with a second non- 67076, 67102, 44181, 67084FL, or 67084alt protein; (vii) modulation of substrate or target molecule location (e.g., modulation of phospholipid location within a cell and/or location with respect to a cellular membrane); (viii) maintenance of aminophospholipid gradients; (ix) modulation of intra- or intercellular signaling and/or gene transcription (e.g., either directly or indirectly); and/or (x) modulation of cellular proliferation, growth, differentiation, apoptosis, absorption, or secretion.

[0286] The isolated nucleic acid molecules of the invention can be used, for example, to express 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides (e.g., via a recombinant expression vector in a host cell in gene therapy applications), to detect 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA (e.g., in a biological sample) or a genetic alteration in a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, and to modulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity, as described further below. The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can be used to treat disorders characterized by insufficient or excessive production of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate or production or transport of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt inhibitors, for example, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt associated disorders.

[0287] As used herein, a “sugar transporter” includes a protein or polypeptide which is involved in transporting a molecule, e.g., a monosaccharide such as D-glucose, D-fructose, D-galactose or mannose, across the plasma membrane of a cell, e.g., a liver cell, fat cell, muscle cell, or blood cell, such as an erythrocyte. Sugar transporters regulate sugar homeostasis in a cell and, typically, have sugar substrate specificity. Examples of sugar transporters include glucose transporters, fructose transporters, and galactose transporters.

[0288] As used herein, a “sugar transporter mediated activity” includes an activity which involves a sugar transporter, e.g., a sugar transporter in a liver cell, fat cell, muscle cell, or blood cell, such as an erythrocyte. Sugar transporter mediated activities include the transport of sugars, e.g., D-glucose, D-fructose, D-galactose or mannose, into and out of cells; the stimulation of molecules that regulate glucose homeostasis (e.g., insulin and glucagon), from cells, e.g., pancreatic cells; and the participation in signal transduction pathways associated with sugar metabolism.

[0289] As the 8099 and 46455 molecules of the present invention are sugar transporters, they may be useful for developing novel diagnostic and therapeutic agents for sugar transporter associated disorders. As used herein, the terms “sugar transporter associated disorder” and “8099 and 46455 disorder,” used interchangeably herein, includes a disorder, disease, or condition which is characterized by an aberrant, e.g., upregulated or downregulated, sugar transporter mediated activity. Sugar transporter associated disorders typically result in, e.g., upregulated or downregulated, sugar levels in a cell. Examples of sugar transporter associated disorders include disorders associated with sugar homeostasis, such as obesity, anorexia, type-1 diabetes, type-2 diabetes, hypoglycemia, glycogen storage disease (Von Gierke disease), type I glycogenosis, bipolar disorder, seasonal affective disorder, and cluster B personality disorders.

[0290] As used interchangeably herein, a “potassium channel associated disorder” or a “54414 or 53763 associated disorder” include a disorder, disease or condition which is caused or characterized by a misregulation (e.g., downregulation or upregulation) of 54414 or 53763 activity. 54414 or 53763 associated disorders can detrimentally affect cellular functions such as cellular proliferation, growth, differentiation, inter- or intra-cellular communication; tissue function, such as cardiac function or musculoskeletal function; systemic responses in an organism, such as nervous system responses, hormonal responses (e.g., insulin response), or immune responses; and protection of cells from toxic compounds (e.g., carcinogens, toxins, or mutagens).

[0291] In a preferred embodiment, 54414 or 53763 associated disorders include CNS disorders such as cognitive and neurodegenerative disorders, examples of which include, but are not limited to, Alzheimer's disease, dementias related to Alzheimer's disease (such as Pick's disease), Parkinson's and other Lewy diffuse body diseases, senile dementia, Huntington's disease, Gilles de la Tourette's syndrome, multiple sclerosis, amyotrophic lateral sclerosis, progressive supranuclear palsy, epilepsy, seizure disorders, and Jakob-Creutzfieldt disease; autonomic function disorders such as hypertension and sleep disorders, and neuropsychiatric disorders, such as depression, schizophrenia, schizoaffective disorder, korsakoff's psychosis, mania, anxiety disorders, or phobic disorders; learning or memory disorders, e.g., amnesia or age-related memory loss, attention deficit disorder, dysthymic disorder, major depressive disorder, mania, obsessive-compulsive disorder, psychoactive substance use disorders, anxiety, phobias, panic disorder, as well as bipolar affective disorder, e.g., severe bipolar affective (mood) disorder (BP-1), and bipolar affective neurological disorders, e.g., migraine and obesity. Further CNS-related disorders include, for example, those listed in the American Psychiatric Association's Diagnostic and Statistical manual of Mental Disorders (DSM), the most current version of which is incorporated herein by reference in its entirety.

[0292] 54414 or 53763 associated disorders also include cellular proliferation, growth, differentiation, or apoptosis disorders. Cellular proliferation, growth, differentiation, or apoptosis disorders include those disorders that affect cell proliferation, growth, differentiation, or apoptosis processes. As used herein, a “cellular proliferation, growth, differentiation, or apoptosis process” is a process by which a cell increases in number, size or content, by which a cell develops a specialized set of characteristics which differ from that of other cells, or by which a cell undergoes programmed cell death. The 54414 or 53763 molecules of the present invention may modulate cellular growth, proliferation, differentiation, or apoptosis, and may play a role in disorders characterized by aberrantly regulated growth, proliferation, differentiation, or apoptosis. Such disorders include cancer, e.g., carcinoma, sarcoma, or leukemia; tumor angiogenesis and metastasis; skeletal dysplasia; hepatic disorders; and hematopoietic and/or myeloproliferative disorders.

[0293] Further examples of 54414 or 53763 associated disorders include cardiac-related disorders. Cardiovascular system disorders in which the 54414 or 53763 molecules of the invention may be directly or indirectly involved include arteriosclerosis, ischemia reperfusion injury, restenosis, arterial inflammation, vascular wall remodeling, ventricular remodeling, rapid ventricular pacing, coronary microembolism, tachycardia, bradycardia, pressure overload, aortic bending, coronary artery ligation, vascular heart disease, atrial fibrilation, Jervell syndrome, Lange-Nielsen syndrome, long-QT syndrome, congestive heart failure, sinus node dysfunction, angina, heart failure, hypertension, atrial fibrillation, atrial flutter, dilated cardiomyopathy, idiopathic cardiomyopathy, myocardial infarction, coronary artery disease, coronary artery spasm, and arrhythmia. 54414 or 53763 associated disorders also include disorders of the musculoskeletal system such as paralysis and muscle weakness, e.g., ataxia, myotonia, and myokymia.

[0294] 54414 or 53763 associated or related disorders also include hormonal disorders, such as conditions or diseases in which the production and/or regulation of hormones in an organism is aberrant. Examples of such disorders and diseases include type I and type II diabetes mellitus, pituitary disorders (e.g., growth disorders), thyroid disorders (e.g., hypothyroidism or hyperthyroidism), and reproductive or fertility disorders (e.g., disorders which affect the organs of the reproductive system, e.g., the prostate gland, the uterus, or the vagina; disorders which involve an imbalance in the levels of a reproductive hormone in a subject; disorders affecting the ability of a subject to reproduce; and disorders affecting secondary sex characteristic development, e.g., adrenal hyperplasia).

[0295] 54414 or 53763 associated or related disorders also include immune disorders, such as autoimmune disorders or immune deficiency disorders, e.g., congenital X-linked infantile hypogammaglobulinemia, transient hypogammaglobulinemia, common variable immunodeficiency, selective IgA deficiency, chronic mucocutaneous candidiasis, or severe combined immunodeficiency.

[0296] As used interchangeably herein, a “phospholipid transporter associated disorder” or a “67076, 67102, 44181, 67084FL, or 67084alt associated disorder” includes a disorder, disease or condition which is caused or characterized by a misregulation (e.g., downregulation or upregulation) of 67076, 67102, 44181, 67084FL, or 67084alt activity. 67076, 67102, 44181, 67084FL, or 67084alt associated disorders can detrimentally affect cellular functions such as cellular proliferation, growth, differentiation, inter- or intra-cellular communication; tissue function, such as cardiac function or musculoskeletal function; systemic responses in an organism, such as nervous system responses, hormonal responses (e.g., insulin response), or immune responses; and protection of cells from toxic compounds (e.g., carcinogens, toxins, or mutagens). Examples of 67076, 67102, 44181, 67084FL, or 67084alt associated disorders include CNS disorders such as cognitive and neurodegenerative disorders, examples of which include, but are not limited to, Alzheimer′ s disease, dementias related to Alzheimer's disease (such as Pick's disease), Parkinson's and other Lewy diffuse body diseases, senile dementia, Huntington's disease, Gilles de la Tourette's syndrome, multiple sclerosis, amyotrophic lateral sclerosis, progressive supranuclear palsy, epilepsy, seizure disorders, and Jakob-Creutzfieldt disease; autonomic function disorders such as hypertension and sleep disorders, and neuropsychiatric disorders, such as depression, schizophrenia, schizoaffective disorder, korsakoff s psychosis, mania, anxiety disorders, or phobic disorders; learning or memory disorders, e.g., amnesia or age-related memory loss, attention deficit disorder, dysthymic disorder, major depressive disorder, mania, obsessive-compulsive disorder, psychoactive substance use disorders, anxiety, phobias, panic disorder, as well as bipolar affective disorder, e.g., severe bipolar affective (mood) disorder (BP-1), and bipolar affective neurological disorders, e.g., migraine and obesity. Further CNS-related disorders include, for example, those listed in the American Psychiatric Association's Diagnostic and Statistical manual of Mental Disorders (DSM), the most current version of which is incorporated herein by reference in its entirety.

[0297] Further examples of 67076, 67102, 44181, 67084FL, or 67084alt associated disorders include cardiac-related disorders. Cardiovascular system disorders in which the 67076, 67102, 44181, 67084FL, or 67084alt molecules of the invention may be directly or indirectly involved include arteriosclerosis, ischemia reperfusion injury, restenosis, arterial inflammation, vascular wall remodeling, ventricular remodeling, rapid ventricular pacing, coronary microembolism, tachycardia, bradycardia, pressure overload, aortic bending, coronary artery ligation, vascular heart disease, atrial fibrilation, Jervell syndrome, Lange-Nielsen syndrome, long-QT syndrome, congestive heart failure, sinus node dysfunction, angina, heart failure, hypertension, atrial fibrillation, atrial flutter, dilated cardiomyopathy, idiopathic cardiomyopathy, myocardial infarction, coronary artery disease, coronary artery spasm, and arrhythmia. 67076, 67102, 44181, 67084FL, or 67084alt associated disorders also include disorders of the musculoskeletal system such as paralysis and muscle weakness, e.g., ataxia, myotonia, and myokymia.

[0298] 67076, 67102, 44181, 67084FL, or 67084alt associated disorders also include cellular proliferation, growth, or differentiation disorders. Cellular proliferation, growth, or differentiation disorders include those disorders that affect cell proliferation, growth, or differentiation processes. As used herein, a “cellular proliferation, growth, or differentiation process” is a process by which a cell increases in number, size or content, or by which a cell develops a specialized set of characteristics which differ from that of other cells. The

[0299] 67076, 67102, 44181, 67084FL, or 67084alt molecules of the present invention are involved in phospholipid transport mechanisms, which are known to be involved in cellular growth, proliferation, and differentiation processes. Thus, the 67076, 67102, 44181, 67084FL, or 67084alt molecules may modulate cellular growth, proliferation, or differentiation, and may play a role in disorders characterized by aberrantly regulated growth, proliferation, or differentiation. Such disorders include cancer, e.g., carcinoma, sarcoma, or leukemia; tumor angiogenesis and metastasis; skeletal dysplasia; hepatic disorders; and hematopoietic and/or myeloproliferative disorders.

[0300] 67076, 67102, 44181, 67084FL, or 67084alt associated or related disorders also include hormonal disorders, such as conditions or diseases in which the production and/or regulation of hormones in an organism is aberrant. Examples of such disorders and diseases include type I and type II diabetes mellitus, pituitary disorders (e.g., growth disorders), thyroid disorders (e.g., hypothyroidism or hyperthyroidism), and reproductive or fertility disorders (e.g, disorders which affect the organs of the reproductive system, e.g., the prostate gland, the uterus, or the vagina; disorders which involve an imbalance in the levels of a reproductive hormone in a subject; disorders affecting the ability of a subject to reproduce; and disorders affecting secondary sex characteristic development, e.g., adrenal hyperplasia).

[0301] 67076, 67102, 44181, 67084FL, or 67084alt associated or related disorders also include immune disorders, such as autoimmune disorders or immune deficiency disorders, e.g., congenital X-linked infantile hypogammaglobulinemia, transient hypogammaglobulinemia, common variable immunodeficiency, selective IgA deficiency, chronic mucocutaneous candidiasis, or severe combined immunodeficiency.

[0302] 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt associated or related disorders also include disorders affecting tissues in which 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt protein is expressed.

[0303] In addition, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can be used to screen for naturally occurring 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrates, to screen for drugs or compounds which modulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity, as well as to treat disorders characterized by insufficient or excessive production of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or production of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide forms which have decreased, aberrant or unwanted activity compared to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt wild type polypeptide (e.g., sugar transporter associated disorder, potassium channel associated diosrders, a phospholipid transporter-associated disorders). Moreover, the anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies of the invention can be used to detect and isolate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, to regulate the bioavailability of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, and modulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity.

[0304] A. Screening Assays

[0305] The invention provides a method (also referred to herein as a “screening assay”) for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) which bind to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides, have a stimulatory or inhibitory effect on, for example, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity, or have a stimulatory or inhibitory effect on, for example, the expression or activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate.

[0306] In one embodiment, the invention provides assays for screening candidate or test compounds which are substrates of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or polypeptide or biologically active portion thereof. In another embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or polypeptide or biologically active portion thereof. The test compounds of the present invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the ‘one-bead one-compound’ library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds (Lam, K. S. (1997) Anticancer Drug Des. 12:145).

[0307] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90:6909; Erb et al. (1994) Proc. Natl. Acad. Sci. USA 91:11422; Zuckermann et al. (1994). J. Med. Chem. 37:2678; Cho et al. (1993) Science 261:1303; Carrell et al. (1994) Angew. Chem. Int. Ed. Engl. 33:2059; Carell et al. (1994) Angew. Chem. Int. Ed. Engl. 33:2061; and in Gallop et al. (1994) J. Med. Chem. 37:1233.

[0308] Libraries of compounds may be presented in solution (e.g., Houghten (1992) Biotechniques 13:412-421), or on beads (Lam (1991) Nature 354:82-84), chips (Fodor (1993) Nature 364:555-556), bacteria (Ladner U.S. Pat. No. 5,223,409), spores (Ladner U.S. Pat. No. '409), plasmids (Cull et al. (1992) Proc Natl Acad Sci USA 89:1865-1869) or on phage (Scott and Smith (1990) Science 249:386-390); (Devlin (1990) Science 249:404-406); (Cwirla et al. (1990) Proc. Natl. Acad Sci. 87:6378-6382); (Felici (1991) J. Mol. Biol. 222:301-310); (Ladner supra.).

[0309] In one embodiment, an assay is a cell-based assay in which a cell which expresses a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or biologically active portion thereof is contacted with a test compound and the ability of the test compound to modulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity is determined.

[0310] Determining the ability of the test compound to modulate 8099 or 46455 activity can be accomplished by monitoring, for example, intracellular or extracellular D-glucose, D-fructose, D-galactose, and/or mannose concentration, or insulin or glucagon secretion. The cell, for example, can be of mammalian origin, e.g., a liver cell, fat cell, muscle cell, or a blood cell, such as an erythrocyte.

[0311] Determining the ability of the test compound to modulate 54414 or 53763 activity can be accomplished by monitoring, for example, potassium current, neurotransmitter release, and/or membrane excitability in a cell which expresses 54414 or 53763. The cell, for example, can be of mammalian origin, e.g., a neuronal cell.

[0312] Determining the ability of the test compound to modulate 67076, 67102, 44181, 67084FL, or 67084alt activity can be accomplished by monitoring, for example, (i) interaction of 67076, 67102, 44181, 67084FL, or 67084alt with a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., a phospholipid, ATP, or a non-67076, 67102, 44181, 67084FL, or 67084alt protein); (ii) transport of a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule (e.g., an aminophospholipid such as phosphatidylserine or phosphatidylethanolamine) from one side of a cellular membrane to the other; (iii) the ability of 67076, 67102, 44181, 67084FL, or 67084alt to be phosphorylated or dephosphorylated; (iv) adoption by 67076, 67102, 44181, 67084FL, or 67084alt of an E1 conformation or an E2 conformation; (v) conversion of a 67076, 67102, 44181, 67084FL, or 67084alt substrate or target molecule to a product (e.g., hydrolysis of ATP); (vi) interaction of 67076, 67102, 44181, 67084FL, or 67084alt with a second non-67076, 67102, 44181, 67084FL, or 67084alt protein; (vii) modulation of substrate or target molecule location (e.g., modulation of phospholipid location within a cell and/or location with respect to a cellular membrane); (viii) maintenance of aminophospholipid gradients; (ix) modulation of intra- or intercellular signaling and/or gene transcription (e.g., either directly or indirectly); and/or (x) modulation of cellular proliferation, growth, differentiation, apoptosis, absorption, and/or secretion.

[0313] The ability of the test compound to modulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt binding to a substrate or to bind to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can also be determined. Determining the ability of the test compound to modulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt binding to a substrate can be accomplished, for example, by coupling the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate with a radioisotope or enzymatic label such that binding of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be determined by detecting the labeled 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate in a complex. Alternatively, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt could be coupled with a radioisotope or enzymatic label to monitor the ability of a test compound to modulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt binding to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate in a complex. Determining the ability of the test compound to bind 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be accomplished, for example, by coupling the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate with a radioisotope or enzymatic label such that binding of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be determined by detecting the labeled 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate in a complex. Alternatively, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt could be coupled with a radioisotope or enzymatic label to monitor the ability of a test compound to modulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt binding to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate in a complex. Determining the ability of the test compound to bind 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be accomplished, for example, by coupling the compound with a radioisotope or enzymatic label such that binding of the compound to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be determined by detecting the labeled 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt compound in a complex. For example, compounds (e.g., 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrates) can be labeled with ¹²⁵I, ³⁵S, ¹⁴C, or ³H, either directly or indirectly, and the radioisotope detected by direct counting of radioemmission or by scintillation counting. Alternatively, compounds can be enzymatically labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product.

[0314] It is also within the scope of this invention to determine the ability of a compound (e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate) to interact with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt without the labeling of any of the interactants. For example, a microphysiometer can be used to detect the interaction of a compound with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt without the labeling of either the compound or the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. McConnell, H. M. et al. (1992) Science 257:1906-1912. As used herein, a “microphysiometer” (e.g., Cytosensor) is an analytical instrument that measures the rate at which a cell acidifies its environment using a light-addressable potentiometric sensor (LAPS). Changes in this acidification rate can be used as an indicator of the interaction between a compound and 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt.

[0315] In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule (e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate) with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule. Determining the ability of the test compound to modulate the activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule can be accomplished, for example, by determining the cellular location of the target molecule, or by determining whether the target molecule (e.g., ATP) has been hydrolyzed.

[0316] Determining the ability of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, or a biologically active fragment thereof, to bind to or interact with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule can be accomplished by one of the methods described above for determining direct binding. In a preferred embodiment, determining the ability of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to bind to or interact with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting the cellular location of target molecule, detecting catalytic/enzymatic activity of the target molecule upon an appropriate substrate, detecting induction of a metabolite of the target molecule (e.g., detecting the products of ATP hydrolysis, changes in intracellular K⁺ levels) detecting the induction of a reporter gene (comprising a target-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a target-regulated cellular response (i.e., membrane excitability, or cell growth, proliferation, differentiation, or apoptosis, sugar transport).

[0317] In yet another embodiment, an assay of the present invention is a cell-free assay in which a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or biologically active portion thereof is contacted with a test compound and the ability of the test compound to bind to the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or biologically active portion thereof is determined. Preferred biologically active portions of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides to be used in assays of the present invention include fragments which participate in interactions with non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt 3 molecules, e.g., fragments with high surface probability scores (see, for example, FIGS. 2, 9, 13, 17, 21, 25, 29, 33, and 37). Binding of the test compound to the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be determined either directly or indirectly as described above. In a preferred embodiment, the assay includes contacting the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or biologically active portion thereof with a known compound which binds 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, wherein determining the ability of the test compound to interact with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide comprises determining the ability of the test compound to preferentially bind to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt or biologically active portion thereof as compared to the known compound.

[0318] In another embodiment, the assay is a cell-free assay in which a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or biologically active portion thereof is contacted with a test compound and the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or biologically active portion thereof is determined. Determining the ability of the test compound to modulate the activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be accomplished, for example, by determining the ability of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to bind to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule by one of the methods described above for determining direct binding. Determining the ability of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to bind to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule can also be accomplished using a technology such as real-time Biomolecular Interaction Analysis (BIA). Sjolander, S. and Urbaniczky, C. (1991) Anal. Chem. 63:2338-2345 and Szabo et al. (1995) Curr. Opin. Struct. Biol. 5:699-705. As used herein, “BIA” is a technology for studying biospecific interactions in real time, without labeling any of the interactants (e.g., BlAcore). Changes in the optical phenomenon of surface plasmon resonance (SPR) can be used as an indication of real-time reactions between biological molecules.

[0319] In an alternative embodiment, determining the ability of the test compound to modulate the activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be accomplished by determining the ability of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to further modulate the activity of a downstream effector of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule. For example, the activity of the effector molecule on an appropriate target can be determined or the binding of the effector to an appropriate target can be determined as previously described.

[0320] In yet another embodiment, the cell-free assay involves contacting a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or biologically active portion thereof with a known compound which binds the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, wherein determining the ability of the test compound to interact with the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide comprises determining the ability of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to preferentially bind to or modulate the activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule.

[0321] The cell-free assays of the present invention are amenable to use of both soluble and/or membrane-bound forms of isolated proteins (e.g., 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt proteins or biologically active portions thereof). In the case of cell-free assays in which a membrane-bound form of an isolated protein is used it may be desirable to utilize a solubilizing agent such that the membrane-bound form of the isolated protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether)_(n), 3-[(3-cholamidopropyl)dimethylamminio]-11-propane sulfonate (CHAPS), 3-[(3-cholamidopropyl)dimethylamminio]-2-hydroxy-1-propane sulfonate (CHAPSO), or N-dodecyl=N,N-dimethyl-3-ammonio-1-propane sulfonate.

[0322] In more than one embodiment of the above assay methods of the present invention, it may be desirable to immobilize either 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, or interaction of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided which adds a domain that allows one or both of the proteins to be bound to a matrix. For example, glutathione-S-transferase/8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt fusion proteins or glutathione-S-transferase/target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or glutathione derivatized micrometer plates, which are then combined with the test compound or the test compound and either the non-adsorbed target protein or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, and the mixture incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or micrometer plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described above. Alternatively, the complexes can be dissociated from the matrix, and the level of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt binding or activity determined using standard techniques.

[0323] Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, substrate, or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques known in the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or target molecules but which do not interfere with binding of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide to its target molecule can be derivatized to the wells of the plate, and unbound target or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or target molecule, as well as enzyme-linked assays which rely on detecting an enzymatic activity associated with the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or target molecule.

[0324] In another embodiment, modulators of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide in the cell is determined. The level of expression of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide in the presence of the candidate compound is compared to the level of expression of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide in the absence of the candidate compound. The candidate compound can then be identified as a modulator of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression based on this comparison. For example, when expression of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide is greater (statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide expression. Alternatively, when expression of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide expression. The level of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide expression in the cells can be determined by methods described herein for detecting 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or polypeptide.

[0325] In yet another aspect of the invention, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides can be used as “bait proteins” in a two-hybrid assay or three-hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos et al. (1993) Cell 72:223-232; Madura et al. (1993) J. Biol. Chem. 268:12046-12054; Bartel et al. (1993) Biotechniques 14:920-924; Iwabuchi et al. (1993) Oncogene 8:1693-1696; and Brent W094/10300), to identify other proteins, which bind to or interact with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt (“8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-binding proteins” or “8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-bp”) and are involved in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity. Such 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-binding proteins are also likely to be involved in the propagation of signals by the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptides or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt targets as, for example, downstream elements of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-mediated signaling pathway. Alternatively, such 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-binding proteins are likely to be 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt inhibitors.

[0326] The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) which is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene which encodes the protein which interacts with the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide.

[0327] In another aspect, the invention pertains to a combination of two or more of the assays described herein. For example, a modulating agent can be identified using a cell-based or a cell free assay, and the ability of the agent to modulate the activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide can be confirmed in vivo, e.g., in an animal such as an animal model for cellular transformation and/or tumorigenesis.

[0328] This invention further pertains to novel agents identified by the above-described screening assays. Accordingly, it is within the scope of this invention to further use an agent identified as described herein in an appropriate animal model. For example, an agent identified as described herein (e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt modulating agent, an antisense 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecule, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-specific antibody, or a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-binding partner) can be used in an animal model to determine the efficacy, toxicity, or side effects of treatment with such an agent. Alternatively, an agent identified as described herein can be used in an animal model to determine the mechanism of action of such an agent. Furthermore, this invention pertains to uses of novel agents identified by the above-described screening assays for treatments as described herein.

[0329] B. Detection Assays

[0330] Portions or fragments of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. For example, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. These applications are described in the subsections below.

[0331] 1. Chromosome Mapping

[0332] Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences, described herein, can be used to map the location of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt genes on a chromosome. The mapping of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences to chromosomes is an important first step in correlating these sequences with genes associated with disease.

[0333] Briefly, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences. Computer analysis of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences can be used to predict primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences will yield an amplified fragment.

[0334] Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but human cells can, the one human chromosome that contains the gene encoding the needed enzyme, will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes (D′Eustachio P. et al. (1983) Science 220:919-924). Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.

[0335] PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences to design oligonucleotide primers, sublocalization can be achieved with panels of fragments from specific chromosomes. Other mapping strategies which can similarly be used to map a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence to its chromosome include in situ hybridization (described in Fan, Y. et al. (1990) Proc. Natl. Acad. Sci. USA, 87:6223-27), pre-screening with labeled flow-sorted chromosomes, and pre-selection by hybridization to chromosome specific cDNA libraries.

[0336] Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal spread can further be used to provide a precise chromosomal location in one step. Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical such as colcemid that disrupts the mitotic spindle. The chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually. The FISH technique can be used with a DNA sequence as short as 500 or 600 bases. However, clones larger than 1,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1,000 bases, and more preferably 2,000 bases will suffice to get good results at a reasonable amount of time. For a review of this technique, see Verma et al., Human Chromosomes: A Manual of Basic Techniques (Pergamon Press, New York 1988).

[0337] Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents corresponding to noncoding regions of the genes actually are preferred for mapping purposes. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping.

[0338] Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. (Such data are found, for example, in V. McKusick, Mendelian Inheritance in Man, available on-line through Johns Hopkins University Welch Medical Library). The relationship between a gene and a disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, for example, Egeland, J. et al. (1987) Nature, 325:783-787.

[0339] Moreover, differences in the DNA sequences between individuals affected and unaffected with a disease associated with the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, can be determined. If a mutation is observed in some or all of the affected individuals but not in any unaffected individuals, then the mutation is likely to be the causative agent of the particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymorphisms.

[0340] 2. Tissue Typing

[0341] The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequences of the present invention can also be used to identify individuals from minute biological samples. The United States military, for example, is considering the use of restriction fragment length polymorphism (RFLP) for identification of its personnel. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. This method does not suffer from the current limitations of “Dog Tags” which can be lost, switched, or stolen, making positive identification difficult. The sequences of the present invention are useful as additional DNA markers for RFLP (described in U.S. Pat. 5,272,057).

[0342] Furthermore, the sequences of the present invention can be used to provide an alternative technique which determines the actual base-by-base DNA sequence of selected portions of an individual's genome. Thus, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences described herein can be used to prepare two PCR primers from the 5′ and 3′ ends of the sequences. These primers can then be used to amplify an individual's DNA and subsequently sequence it.

[0343] Panels of corresponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences of the present invention can be used to obtain such identification sequences from individuals and from tissue. The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences of the invention uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences of SEQ ID NO:1 or SEQ ID NO:4 can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers which each yield a noncoding amplified sequence of 100 bases. If predicted coding sequences, such as those in SEQ ID NO:3 or SEQ ID NO:6 are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0344] If a panel of reagents from 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences described herein is used to generate a unique identification database for an individual, those same reagents can later be used to identify tissue from that individual. Using the unique identification database, positive identification of the individual, living or dead, can be made from extremely small tissue samples.

[0345] 3. Use of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt Sequences in Forensic Biology

[0346] DNA-based identification techniques can also be used in forensic biology. Forensic biology is a scientific field employing genetic typing of biological evidence found at a crime scene as a means for positively identifying, for example, a perpetrator of a crime. To make such an identification, PCR technology can be used to amplify DNA sequences taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, or semen found at a crime scene. The amplified sequence can then be compared to a standard, thereby allowing identification of the origin of the biological sample.

[0347] The sequences of the present invention can be used to provide polynucleotide reagents, e.g., PCR primers, targeted to specific loci in the human genome, which can enhance the reliability of DNA-based forensic identifications by, for example, providing another “identification marker” (i.e. another DNA sequence that is unique to a particular individual). As mentioned above, actual base sequence information can be used for identification as an accurate alternative to patterns formed by restriction enzyme generated fragments. Sequences targeted to noncoding regions of SEQ ID NO:1 or SEQ ID NO:4 are particularly appropriate for this use as greater numbers of polymorphisms occur in the noncoding regions, making it easier to differentiate individuals using this technique. Examples of polynucleotide reagents include the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences or portions thereof, e.g., fragments derived from the noncoding regions of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, or SEQ ID NO:13, having a length of at least 20 bases, preferably at least 30 bases.

[0348] The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleotide sequences described herein can further be used to provide polynucleotide reagents, e.g., labeled or labelable probes which can be used in, for example, an in situ hybridization technique, to identify a specific tissue, e.g., brain tissue. This can be very useful in cases where a forensic pathologist is presented with a tissue of unknown origin. Panels of such 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt probes can be used to identify tissue by species and/or by organ type.

[0349] In a similar fashion, these reagents, e.g., 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt primers or probes can be used to screen tissue culture for contamination (i.e. screen for the presence of a mixture of different types of cells in a culture).

[0350] C. Predictive Medicine:

[0351] The present invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the present invention relates to diagnostic assays for determining 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide and/or nucleic acid expression as well as 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, nucleic acid expression or activity. For example, mutations in a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, nucleic acid expression or activity.

[0352] Another aspect of the invention pertains to monitoring the influence of agents (e.g. drugs, compounds) on the expression or activity of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt in clinical trials.

[0353] These and other agents are described in further detail in the following sections.

[0354] 1. Diagnostic Assays

[0355] An exemplary method for detecting the presence or absence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid (e.g., mRNA, or genomic DNA) that encodes 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide such that the presence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid is detected in the biological sample. In another aspect, the present invention provides a method for detecting the presence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity in a biological sample by contacting the biological sample with an agent capable of detecting an indicator of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity such that the presence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity is detected in the biological sample. A preferred agent for detecting 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or genomic DNA. The nucleic acid probe can be, for example, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid set forth in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or the DNA insert of the plasmid deposited with ATCC as Accession Number ______, ______, ______, ______, or ______, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.

[0356] A preferred agent for detecting 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide is an antibody capable of binding to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab′)2) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA, polypeptide, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations and immunofluorescence. In vitro techniques for detection of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of PLTR polypeptide include introducing into a subject a labeled 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

[0357] The present invention also provides diagnostic assays for identifying the presence or absence of a genetic alteration characterized by at least one of (i) aberrant modification or mutation of a gene encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide; (ii) aberrant expression of a gene encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide; (iii) mis-regulation of the gene; and (iii) aberrant post-translational modification of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, wherein a wild-type form of the gene encodes a polypeptide with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity. “Misexpression or aberrant expression”, as used herein, refers to a non-wild type pattern of gene expression, at the RNA or protein level. It includes, but is not limited to, expression at non-wild type levels (e.g., over or under expression); a pattern of expression that differs from wild type in terms of the time or stage at which the gene is expressed (e.g., increased or decreased expression (as compared with wild type) at a predetermined developmental period or stage); a pattern of expression that differs from wild type in terms of decreased expression (as compared with wild type) in a predetermined cell type or tissue type; a pattern of expression that differs from wild type in terms of the splicing size, amino acid sequence, post-transitional modification, or biological activity of the expressed polypeptide; a pattern of expression that differs from wild type in terms of the effect of an environmental stimulus or extracellular stimulus on expression of the gene (e.g., a pattern of increased or decreased expression (as compared with wild type) in the presence of an increase or decrease in the strength of the stimulus).

[0358] In one embodiment, the biological sample contains protein molecules from the test subject. Alternatively, the biological sample can contain mRNA molecules from the test subject or genomic DNA molecules from the test subject. A preferred biological sample is a serum sample isolated by conventional means from a subject.

[0359] In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, mRNA, or genomic DNA, such that the presence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, mRNA or genomic DNA in the control sample with the presence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, mRNA or genomic DNA in the test sample.

[0360] The invention also encompasses kits for detecting the presence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt in a biological sample. For example, the kit can comprise a labeled compound or agent capable of detecting 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or mRNA in a biological sample; means for determining the amount of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt in the sample; and means for comparing the amount of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid.

[0361] 2. Prognostic Assays

[0362] The diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity. As used herein, the term “aberrant” includes a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity which deviates from the wild type 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity. Aberrant expression or activity includes increased or decreased expression or activity, as well as expression or activity which does not follow the wild type developmental pattern of expression or the subcellular pattern of expression. For example, aberrant 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity is intended to include the cases in which a mutation in the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene causes the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene to be under-expressed or over-expressed and situations in which such mutations result in a non-functional 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or a polypeptide which does not function in a wild-type fashion, e.g., a protein which does not interact with or transport a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate, or one which interacts with or transports a non-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate. As used herein, the term “unwanted” includes an unwanted phenomenon involved in a biological response such as deregulated cellular proliferation. For example, the term unwanted includes a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity which is undesirable in a subject.

[0363] The assays described herein, such as the preceding diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with a misregulation in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide activity or nucleic acid expression, such as a as a cell growth, proliferation and/or differentiation disorder. Alternatively, the prognostic assays can be utilized to identify a subject having or at risk for developing a disorder associated with a misregulation in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide activity or nucleic acid expression, such as a cell growth, proliferation and/or differentiation disorder, a sugar trnasporter associated disorder, or a potassium channel associated disorder, as described herein. Thus, the present invention provides a method for identifying a disease or disorder associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity in which a test sample is obtained from a subject and 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid (e.g., mRNA or genomic DNA) is detected, wherein the presence of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid is diagnostic for a subject having or at risk of developing a disease or disorder associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity. As used herein, a “test sample” refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid (e.g., serum), cell sample, or tissue.

[0364] Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity. For example, such methods can be used to determine whether a subject can be effectively treated with an agent for a sugar transporter-associated disorder, a potassium channel associated disorder, or phospholipid transporter-associated disorder. Thus, the present invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity in which a test sample is obtained and 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid expression or activity is detected (e.g., wherein the abundance of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid expression or activity is diagnostic for a subject that can be administered the agent to treat a disorder associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity).

[0365] The methods of the invention can also be used to detect genetic alterations in a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, thereby determining if a subject with the altered gene is at risk for a disorder characterized by misregulation in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide activity or nucleic acid expression, such as a cell growth, proliferation and/or differentiation disorder. In preferred embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic alteration characterized by at least one of an alteration affecting the integrity of a gene encoding a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-polypeptide, or the mis-expression of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene. For example, such genetic alterations can be detected by ascertaining the existence of at least one of 1) a deletion of one or more nucleotides from a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene; 2) an addition of one or more nucleotides to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene; 3) a substitution of one or more nucleotides of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, 4) a chromosomal rearrangement of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene; 5) an alteration in the level of a messenger RNA transcript of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, 6) aberrant modification of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, such as of the methylation pattern of the genomic DNA, 7) the presence of a non-wild type splicing pattern of a messenger RNA transcript of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, 8) a non-wild type level of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-polypeptide, 9) allelic loss of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, and 10) inappropriate post-translational modification of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-polypeptide. As described herein, there are a large number of assays known in the art which can be used for detecting alterations in a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene. A preferred biological sample is a tissue or serum sample isolated by conventional means from a subject.

[0366] In certain embodiments, detection of the alteration involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran et al. (1988) Science 241:1077-1080; and Nakazawa et al. (1994) Proc. Natl. Acad. Sci. USA 91:360-364), the latter of which can be particularly useful for detecting point mutations in the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene (see Abravaya et al. (1995) Nucleic Acids Res .23:675-682). This method can include the steps of collecting a sample of cells from a subject, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers which specifically hybridize to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene under conditions such that hybridization and amplification of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.

[0367] Alternative amplification methods include: self sustained sequence replication (Guatelli, J. C. et al., (1990) Proc. Natl. Acad. Sci. USA 87:1874-1878), transcriptional amplification system (Kwoh, D. Y. et al., (1989) Proc. Natl. Acad Sci. USA 86:1173-1177), Q-Beta Replicase (Lizardi, P. M. et al. (1988) Bio-Technology 6:1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.

[0368] In an alternative embodiment, mutations in a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, for example, U.S. Pat. No. 5,498,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.

[0369] In other embodiments, genetic mutations in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high density arrays containing hundreds or thousands of oligonucleotides probes (Cronin, M. T. et al (1996) Human Mutation 7: 244-255; Kozal, M. J. et al. (1996) Nature Medicine 2: 753-759). For example, genetic mutations in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, M. T. et al. supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes. This step allows the identification of point mutations. This step is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.

[0370] In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene and detect mutations by comparing the sequence of the sample 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxam and Gilbert ((1977) Proc. Natl. Acad. Sci. USA 74:560) or Sanger ((1977) Proc. Natl. Acad. Sci. USA 74:5463). It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays ((1995) Biotechniques 19:448), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101; Cohen et al. (1996) Adv. Chromatogr. 36:127-162; and Griffin et al. (1993) Appl. Biochem. Biotechnol. 38:147-159).

[0371] Other methods for detecting mutations in the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes (Myers et al. (1985) Science 230:1242). In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent which cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S1 nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, for example, Cotton et al. (1988) Proc. Natl Acad Sci USA 85:4397; Saleeba et al. (1992) Methods Enzymol. 217:286-295. In a preferred embodiment, the control DNA or RNA can be labeled for detection.

[0372] In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called “DNA mismatch repair” enzymes) in defined systems for detecting and mapping point mutations in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt cDNAs obtained from samples of cells. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches (Hsu et al. (1994) Carcinogenesis 15:1657-1662). According to an exemplary embodiment, a probe based on a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence, e.g., a wild-type 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, for example, U.S. Pat. No. 5,459,039.

[0373] In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt genes. For example, single strand conformation polymorphism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids (Orita et al. (1989) Proc Natl. Acad. Sci USA: 86:2766, see also Cotton (1993) Mutat. Res. 285:125-144; and Hayashi (1992) Genet. Anal. Tech. Appl. 9:73-79). Single-stranded DNA fragments of sample and control 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acids will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In a preferred embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility (Keen et al. (1991) Trends Genet 7:5).

[0374] In yet another embodiment the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE) (Myers et al. (1985) Nature 313:495). When DGGE is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA (Rosenbaum and Reissner (1987) Biophys Chem 265:12753).

[0375] Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions which permit hybridization only if a perfect match is found (Saiki et al. (1986) Nature 324:163); Saiki et al. (1989) Proc. Natl Acad. Sci USA 86:6230). Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.

[0376] Alternatively, allele specific amplification technology which depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization) (Gibbs et al. (1989) Nucleic Acids Res. 17:2437-2448) or at the extreme 3′ end of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (Prossner (1993) Tibtech 11:238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection (Gasparini et al. (1992) Mol. Cell Probes 6:1). It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification (Barany (1991) Proc. Natl. Acad. Sci USA 88:189). In such cases, ligation will occur only if there is a perfect match at the 3′ end of the 5′ sequence making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.

[0377] The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene.

[0378] Furthermore, any cell type or tissue in which 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt is expressed may be utilized in the prognostic assays described herein.

[0379] 3. Monitoring of Effects During Clinical Trials

[0380] Monitoring the influence of agents (e.g., drugs) on the expression or activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide (e.g., the modulation of gene expression, cellular signaling, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity, phospholipid transporter activity, and/or cell growth, proliferation, differentiation, absorption, and/or secretion mechanisms) can be applied not only in basic drug screening, but also in clinical trials. For example, the effectiveness of an agent determined by a screening assay as described herein to increase 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene expression, polypeptide levels, or upregulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity, can be monitored in clinical trials of subjects exhibiting decreased 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene expression, polypeptide levels, or downregulated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity. Alternatively, the effectiveness of an agent determined by a screening assay to decrease 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene expression, polypeptide levels, or downregulate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity, can be monitored in clinical trials of subjects exhibiting increased 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene expression, polypeptide levels, or upregulated 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity. In such clinical trials, the expression or activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene, and preferably, other genes that have been implicated in, for example, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disorder can be used as a “read out” or markers of the phenotype of a particular cell.

[0381] For example, and not by way of limitation, genes, including 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt, that are modulated in cells by treatment with an agent (e.g., compound, drug or small molecule) which modulates 67076, 67102, 44181, 67084FL, or 67084alt activity (e.g., identified in a screening assay as described herein) can be identified.

[0382] Thus, to study the effect of agents on phospholipid transporter-associated disorders (e.g., disorders characterized by deregulated gene expression, cellular signaling, 67076, 67102, 44181, 67084FL, or 67084alt activity, phospholipid transporter activity, and/or cell growth, proliferation, differentiation, absorption, and/or secretion mechanisms), for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of 67076, 67102, 44181, 67084FL, or 67084alt and other genes implicated in the transporter-associated disorder, respectively. The levels of gene expression (e.g., a gene expression pattern) can be quantified by northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of polypeptide produced, by one of the methods as described herein, or by measuring the levels of activity of 67076, 67102, 44181, 67084FL, or 67084alt or other genes. In this way, the gene expression pattern can serve as a marker, indicative of the physiological response of the cells to the agent. Accordingly, this response state may be determined before, and at various points during treatment of the individual with the agent.

[0383] In a preferred embodiment, the present invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) including the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, mRNA, or genomic DNA in the pre-administration sample with the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt to lower levels than detected, i. e. to decrease the effectiveness of the agent. According to such an embodiment, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity may be used as an indicator of the effectiveness of an agent, even in the absence of an observable phenotypic response.

[0384] D. Methods of Treatment:

[0385] The present invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity, e.g. a phospholipid transporter-associated disorder. “Treatment”, as used herein, is defined as the application or administration of a therapeutic agent to a patient, or application or administration of a therapeutic agent to an isolated tissue or cell line from a patient, who has a disease or disorder, a symptom of disease or disorder or a predisposition toward a disease or disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect the disease or disorder, the symptoms of disease or disorder or the predisposition toward a disease or disorder. A therapeutic agent includes, but is not limited to, small molecules, peptides, antibodies, ribozymes and antisense oligonucleotides.

[0386] With regards to both prophylactic and therapeutic methods of treatment, such treatments may be specifically tailored or modified, based on knowledge obtained from the field of pharmacogenomics. “Pharmacogenomics”, as used herein, refers to the application of genomics technologies such as gene sequencing, statistical genetics, and gene expression analysis to drugs in clinical development and on the market. More specifically, the term refers the study of how a patient's genes determine his or her response to a drug (e.g., a patient's “drug response phenotype”, or “drug response genotype”). Thus, another aspect of the invention provides methods for tailoring an individual's prophylactic or therapeutic treatment with either the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecules of the present invention or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt modulators according to that individual's drug response genotype. Pharmacogenomics allows a clinician or physician to target prophylactic or therapeutic treatments to patients who will most benefit from the treatment and to avoid treatment of patients who will experience toxic drug-related side effects.

[0387] 1. Prophylactic Methods

[0388] In one aspect, the invention provides a method for preventing in a subject, a disease or condition associated with an aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity, by administering to the subject a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt or an agent which modulates 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or at least one 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity. Subjects at risk for a disease which is caused or contributed to by aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending on the type of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt aberrancy, for example, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt agonist or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein.

[0389] 2. Therapeutic Methods

[0390] Another aspect of the invention pertains to methods of modulating 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity for therapeutic purposes. Accordingly, in an exemplary embodiment, the modulatory method of the invention involves contacting a cell capable of expressing 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt with an agent that modulates one or more of the activities of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide activity associated with the cell, such that 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity in the cell is modulated. An agent that modulates 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide activity can be an agent as described herein, such as a nucleic acid or a polypeptide, a naturally-occurring target molecule of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide (e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt substrate), a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibody, a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt agonist or antagonist, a peptidomimetic of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt agonist or antagonist, or other small molecule. In one embodiment, the agent stimulates one or more 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activities. Examples of such stimulatory agents include active 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide and a nucleic acid molecule encoding 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt that has been introduced into the cell. In another embodiment, the agent inhibits one or more 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activities. Examples of such inhibitory agents include antisense 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt nucleic acid molecules, anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt 3 antibodies, and 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt inhibitors. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the present invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant or unwanted expression or activity of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., upregulates or downregulates) 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity. In another embodiment, the method involves administering a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or nucleic acid molecule as therapy to compensate for reduced, aberrant, or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression or activity.

[0391] Stimulation of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity is desirable in situations in which 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt is abnormally downregulated and/or in which increased 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity is likely to have a beneficial effect. Likewise, inhibition of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity is desirable in situations in which 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt is abnormally upregulated and/or in which decreased 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity is likely to have a beneficial effect.

[0392] 3. Pharmacogenomics

[0393] The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecules of the present invention, as well as agents, or modulators which have a stimulatory or inhibitory effect on 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity (e.g., 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene expression) as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically), for example, disorders characterized by aberrant 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene expression, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity, membrane excitability or conductance, gene transcription, phospholipid transporter activity, cellular signaling, and/or cell growth, proliferation, differentiation, absorption, and/or secretion disorders associated with aberrant or unwanted 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity. In conjunction with such treatment, pharmacogenomics (ie., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug) may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, a physician or clinician may consider applying knowledge obtained in relevant pharmacogenomics studies in determining whether to administer a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecule or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt modulator as well as tailoring the dosage and/or therapeutic regimen of treatment with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecule or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt modulator.

[0394] Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See, for example, Eichelbaum, M. et al. (1996) Clin. Exp. Pharmacol. Physiol. 23(10-11): 983-985 and Linder, M. W. et al. (1997) Clin. Chem. 43(2):254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drug action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare genetic defects or as naturally-occurring polymorphisms. For example, glucose-6-phosphate dehydrogenase deficiency (G6PD) is a common inherited enzymopathy in which the main clinical complication is haemolysis after ingestion of oxidant drugs (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.

[0395] One pharmacogenomics approach to identifying genes that predict drug response, known as “a genome-wide association”, relies primarily on a high-resolution map of the human genome consisting of already known gene-related markers (e.g., a “bi-allelic” gene marker map which consists of 60,000-100,000 polymorphic or variable sites on the human genome, each of which has two variants.) Such a high-resolution genetic map can be compared to a map of the genome of each of a statistically significant number of patients taking part in a Phase II/III drug trial to identify markers associated with a particular observed drug response or side effect. Alternatively, such a high resolution map can be generated from a combination of some ten-million known single nucleotide polymorphisms (SNPs) in the human genome. As used herein, a “SNP” is a common alteration that occurs in a single nucleotide base in a stretch of DNA. For example, a SNP may occur once per every 1000 bases of DNA. A SNP may be involved in a disease process, however, the vast majority may not be disease-associated. Given a genetic map based on the occurrence of such SNPs, individuals can be grouped into genetic categories depending on a particular pattern of SNPs in their individual genome. In such a manner, treatment regimens can be tailored to groups of genetically similar individuals, taking into account traits that may be common among such genetically similar individuals.

[0396] Alternatively, a method termed the “candidate gene approach”, can be utilized to identify genes that predict drug response. According to this method, if a gene that encodes a drugs target is known (e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide of the present invention), all common variants of that gene can be fairly easily identified in the population and it can be determined if having one version of the gene versus another is associated with a particular drug response.

[0397] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome P450 enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. The other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.

[0398] Alternatively, a method termed the “gene expression profiling”, can be utilized to identify genes that predict drug response. For example, the gene expression of an animal dosed with a drug (e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecule or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt modulator of the present invention) can give an indication whether gene pathways related to toxicity have been turned on.

[0399] Information generated from more than one of the above pharmacogenomics approaches can be used to determine appropriate dosage and treatment regimens for prophylactic or therapeutic treatment an individual. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecule or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt modulator, such as a modulator identified by one of the exemplary screening assays described herein.

[0400] 4. Use of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt Molecules as Surrogate Markers

[0401] The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecules of the invention are also useful as markers of disorders or disease states, as markers for precursors of disease states, as markers for predisposition of disease states, as markers of drug activity, or as markers of the pharmacogenomic profile of a subject. Using the methods described herein, the presence, absence and/or quantity of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecules of the invention may be detected, and may be correlated with one or more biological states in vivo. For example, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecules of the invention may serve as surrogate markers for one or more disorders or disease states or for conditions leading up to disease states. As used herein, a “surrogate marker” is an objective biochemical marker which correlates with the absence or presence of a disease or disorder, or with the progression of a disease or disorder (e.g., with the presence or absence of a tumor). The presence or quantity of such markers is independent of the disease. Therefore, these markers may serve to indicate whether a particular course of treatment is effective in lessening a disease state or disorder. Surrogate markers are of particular use when the presence or extent of a disease state or disorder is difficult to assess through standard methodologies (e.g., early stage tumors), or when an assessment of disease progression is desired before a potentially dangerous clinical endpoint is reached (e.g., an assessment of cardiovascular disease may be made using cholesterol levels as a surrogate marker, and an analysis of HIV infection may be made using HIV RNA levels as a surrogate marker, well in advance of the undesirable clinical outcomes of myocardial infarction or fully-developed AIDS). Examples of the use of surrogate markers in the art include: Koomen et al. (2000) J. Mass. Spectrom. 35: 258-264; and James (1994) AIDS Treatment News Archive 209.

[0402] The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecules of the invention are also useful as pharmacodynamic markers. As used herein, a “pharmacodynamic marker” is an objective biochemical marker which correlates specifically with drug effects. The presence or quantity of a pharmacodynamic marker is not related to the disease state or disorder for which the drug is being administered; therefore, the presence or quantity of the marker is indicative of the presence or activity of the drug in a subject. For example, a pharmacodynamic marker may be indicative of the concentration of the drug in a biological tissue, in that the marker is either expressed or transcribed or not expressed or transcribed in that tissue in relationship to the level of the drug. In this fashion, the distribution or uptake of the drug may be monitored by the pharmacodynamic marker. Similarly, the presence or quantity of the pharmacodynamic marker may be related to the presence or quantity of the metabolic product of a drug, such that the presence or quantity of the marker is indicative of the relative breakdown rate of the drug in vivo. Pharmacodynamic markers are of particular use in increasing the sensitivity of detection of drug effects, particularly when the drug is administered in low doses. Since even a small amount of a drug may be sufficient to activate multiple rounds of marker (e.g., a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt marker) transcription or expression, the amplified marker may be in a quantity which is more readily detectable than the drug itself. Also, the marker may be more easily detected due to the nature of the marker itself; for example, using the methods described herein, anti-8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt antibodies may be employed in an immune-based detection system for a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide marker, or 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-specific radiolabeled probes may be used to detect a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA marker. Furthermore, the use of a pharmacodynamic marker may offer mechanism-based prediction of risk due to drug treatment beyond the range of possible direct observations. Examples of the use of pharmacodynamic markers in the art include: Matsuda et al. US 6,033,862; Hattis et al. (1991) Env. Health Perspect. 90: 229-238; Schentag (1999) Am. J. Health-Syst. Pharm. 56 Suppl. 3: S21-S24; and Nicolau (1999) Am, J. Health-Syst. Pharm. 56 Suppl. 3: S16-S20.

[0403] The 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecules of the invention are also useful as pharmacogenomic markers. As used herein, a “pharmacogenomic marker” is an objective biochemical marker which correlates with a specific clinical drug response or susceptibility in a subject (see, e.g., McLeod et al. (1999) Eur. J. Cancer 35(12): 1650-1652). The presence or quantity of the pharmacogenomic marker is related to the predicted response of the subject to a specific drug or class of drugs prior to administration of the drug. By assessing the presence or quantity of one or more pharmacogenomic markers in a subject, a drug therapy which is most appropriate for the subject, or which is predicted to have a greater degree of success, may be selected. For example, based on the presence or quantity of RNA, or polypeptide (e.g., 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide or RNA) for specific tumor markers in a subject, a drug or course of treatment may be selected that is optimized for the treatment of the specific tumor likely to be present in the subject. Similarly, the presence or absence of a specific sequence mutation in 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt DNA may correlate 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt drug response. The use of pharmacogenomic markers therefore permits the application of the most appropriate treatment for each subject without having to administer the therapy.

[0404] VI. Electronic Apparatus Readable Media and Arrays

[0405] Electronic apparatus readable media comprising 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information is also provided. As used herein, “8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information” refers to any nucleotide and/or amino acid sequence information particular to the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt molecules of the present invention, including but not limited to full-length nucleotide and/or amino acid sequences, partial nucleotide and/or amino acid sequences, polymorphic sequences including single nucleotide polymorphisms (SNPs), epitope sequences, and the like. Moreover, information “related to” said 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information includes detection of the presence or absence of a sequence (e.g., detection of expression of a sequence, fragment, polymorphism, etc.), determination of the level of a sequence (e.g., detection of a level of expression, for example, a quantative detection), detection of a reactivity to a sequence (e.g., detection of protein expression and/or levels, for example, using a sequence-specific antibody), and the like. As used herein, “electronic apparatus readable media” refers to any suitable medium for storing, holding or containing data or information that can be read and accessed directly by an electronic apparatus. Such media can include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as compact disc; electronic storage media such as RAM, ROM, EPROM, EEPROM and the like; general hard disks and hybrids of these categories such as magnetic/optical storage media. The medium is adapted or configured for having recorded thereon 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information of the present invention.

[0406] As used herein, the term “electronic apparatus” is intended to include any suitable computing or processing apparatus or other device configured or adapted for storing data or information. Examples of electronic apparatus suitable for use with the present invention include stand-alone computing apparatus; networks, including a local area network (LAN), a wide area network (WAN) Internet, Intranet, and Extranet; electronic appliances such as a personal digital assistants (PDAs), cellular phone, pager and the like; and local and distributed processing systems.

[0407] As used herein, “recorded” refers to a process for storing or encoding information on the electronic apparatus readable medium. Those skilled in the art can readily adopt any of the presently known methods for recording information on known media to generate manufactures comprising the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information.

[0408] A variety of software programs and formats can be used to store the sequence information on the electronic apparatus readable medium. For example, the sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and MicroSoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like, as well as in other forms. Any number of dataprocessor structuring formats (e.g., text file or database) may be employed in order to obtain or create a medium having recorded thereon the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information.

[0409] By providing 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information in readable form, one can routinely access the sequence information for a variety of purposes. For example, one skilled in the art can use the sequence information in readable form to compare a target sequence or target structural motif with the sequence information stored within the data storage means. Search means are used to identify fragments or regions of the sequences of the invention which match a particular target sequence or target motif.

[0410] The present invention therefore provides a medium for holding instructions for performing a method for determining whether a subject has a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder or a pre-disposition to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder, wherein the method comprises the steps of determining 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information associated with the subject and based on the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information, determining whether the subject has a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder or a pre-disposition to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder and/or recommending a particular treatment for the disease, disorder or pre-disease condition.

[0411] The present invention further provides in an electronic system and/or in a network, a method for determining whether a subject has a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder or a pre-disposition to a disease associated with a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt wherein the method comprises the steps of determining 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information associated with the subject, and based on the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information, determining whether the subject has a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder or a predisposition to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder, and/or recommending a particular treatment for the disease, disorder or pre-disease condition. The method may further comprise the step of receiving phenotypic information associated with the subject and/or acquiring from a network phenotypic information associated with the subject.

[0412] The present invention also provides in a network, a method for determining whether a subject has a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder or a pre-disposition to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder associated with 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt, said method comprising the steps of receiving 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence information from the subject and/or information related thereto, receiving phenotypic information associated with the subject, acquiring information from the network corresponding to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt and/or a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder, and based on one or more of the phenotypic information, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt information (e.g., sequence information and/or information related thereto), and the acquired information, determining whether the subject has a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder or a pre-disposition to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder. The method may further comprise the step of recommending a particular treatment for the disease, disorder or pre-disease condition.

[0413] The present invention also provides a business method for determining whether a subject has a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder or a pre-disposition to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder, said method comprising the steps of receiving information related to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt (e.g., sequence information and/or information related thereto), receiving phenotypic information associated with the subject, acquiring information from the network related to 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt and/or related to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder, and based on one or more of the phenotypic information, the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt information, and the acquired information, determining whether the subject has a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder or a pre-disposition to a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder. The method may further comprise the step of recommending a particular treatment for the disease, disorder or pre-disease condition.

[0414] The invention also includes an array comprising a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt sequence of the present invention. The array can be used to assay expression of one or more genes in the array. In one embodiment, the array can be used to assay gene expression in a tissue to ascertain tissue specificity of genes in the array. In this manner, up to about 7600 genes can be simultaneously assayed for expression, one of which can be 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt. This allows a profile to be developed showing a battery of genes specifically expressed in one or more tissues.

[0415] In addition to such qualitative determination, the invention allows the quantitation of gene expression. Thus, not only tissue specificity, but also the level of expression of a battery of genes in the tissue is ascertainable. Thus, genes can be grouped on the basis of their tissue expression per se and level of expression in that tissue. This is useful, for example, in ascertaining the relationship of gene expression between or among tissues. Thus, one tissue can be perturbed and the effect on gene expression in a second tissue can be determined. In this context, the effect of one cell type on another cell type in response to a biological stimulus can be determined. Such a determination is useful, for example, to know the effect of cell-cell interaction at the level of gene expression. If an agent is administered therapeutically to treat one cell type but has an undesirable effect on another cell type, the invention provides an assay to determine the molecular basis of the undesirable effect and thus provides the opportunity to co-administer a counteracting agent or otherwise treat the undesired effect. Similarly, even within a single cell type, undesirable biological effects can be determined at the molecular level. Thus, the effects of an agent on expression of other than the target gene can be ascertained and counteracted.

[0416] In another embodiment, the array can be used to monitor the time course of expression of one or more genes in the array. This can occur in various biological contexts, as disclosed herein, for example development of a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder, progression of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder, and processes, such a cellular transformation associated with the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-associated disease or disorder.

[0417] The array is also useful for ascertaining the effect of the expression of a gene on the expression of other genes in the same cell or in different cells (e.g., acertaining the effect of 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt expression on the expression of other genes). This provides, for example, for a selection of alternate molecular targets for therapeutic intervention if the ultimate or downstream target cannot be regulated.

[0418] The array is also useful for ascertaining differential expression patterns of one or more genes in normal and abnormal cells. This provides a battery of genes (e.g, including 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt) that could serve as a molecular target for diagnosis or therapeutic intervention.

[0419] This invention is further illustrated by the following examples which should not be construed as limiting. The contents of all references, patents and published patent applications cited throughout this application, as well as the Figures and the Sequence Listing, are incorporated herein by reference.

EXAMPLES Example 1 Identification and Characterization of Human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, and 67084alt cDNAs

[0420] In this example, the identification and characterization of the gene encoding human 8099, 46455, 54414, 53763, 67076, 67102, 44181, full length 67084 (67084FL), and 67084alt is described.

[0421] Isolation of the Human 8099 and 46455 cDNAs

[0422] The invention is based, at least in part, on the discovery of a human gene encoding a novel polypeptide, referred to herein as human 8099. The entire sequence of the human clone 8099 was determined and found to contain an open reading frame termed human “8099.” The nucleotide sequence of the human 8099 gene is set forth in FIGS. 1A-B and in the Sequence Listing as SEQ ID NO:1. The amino acid sequence of the human 8099 expression product is set forth in FIG. 1 and in the Sequence Listing as SEQ ID NO:2. The 8099 polypeptide comprises 617 amino acids. The coding region (open reading frame) of SEQ ID NO:1 is set forth as SEQ ID NO:3. Clone 8099, comprising the coding region of human 8099, was deposited with the American Type Culture Collection (ATCC®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0423] The invention is further based, at least in part, on the discovery of a human gene encoding a novel polypeptide, referred to herein as human 46455. The entire sequence of the human clone 46455 was determined and found to contain an open reading frame termed human “46455.” The nucleotide sequence of the human 46455 gene is set forth in FIG. 4 and in the Sequence Listing as SEQ ID NO:4. The amino acid sequence of the human 46455 expression product is set forth in FIGS. 8A-B and in the Sequence Listing as SEQ ID NO:5. The 46455 polypeptide comprises 528 amino acids. The coding region (open reading frame) of SEQ ID NO:4 is set forth as SEQ ID NO:6. Clone 46455, comprising the coding region of human 46455, was deposited with the American Type Culture Collection (ATCC®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0424] Analysis of the Human 8099 and 46455 Molecules

[0425] A search using the polypeptide sequence of SEQ ID NO:2 was performed against the HMM database in PFAM (FIGS. 3A-B) resulting in the identification of a sugar transporter family domain in the amino acid sequence of human 8099 at about residues 43-564 of SEQ ID NO:2 (score=318.2), a potential FecCD family domain in the amino acid sequence of human 8099 at about residues 26-227 of SEQ ID NO:2 (score=-218.2), and a potential monocarboxylate transporter domain in the amino acid sequence of human 8099 at about residues 29-567 of SEQ ID NO:2 (score=-235.8).

[0426] The amino acid sequence of human 8099 was analyzed using the program PSORT (available through the Prosite website) to predict the localization of the proteins within the cell. This program assesses the presence of different targeting and localization amino acid sequences within the query sequence. The results of this analysis show that human 8099 may be localized to the endoplasmic reticulum or mitochondria.

[0427] Searches of the amino acid sequence of human 8099 were further performed against the Prosite database. These searches resulted in the identification in the amino acid sequence of human 8099 of a number of potential N-glycosylation sites at about amino acid residues 371-374, 383-386, 396-399, 401-404 of SEQ ID NO:2, a number of potential protein kinase C phosphorylation sites at about amino acid residues 220-222, 256-258, 403-405 of SEQ ID NO:2, a number of potential casein kinase II phosphorylation sites at about amino acid residues 18-21, 75-78, 169-172, 246-249, 256-259, 264-267, 385-388, 403-406, 443-446, 520-523 of SEQ ID NO:2, a number of potential N-myristoylation sites at about amino acid residues 51-56, 59-64, 89-94, 141-146, 165-170, 178-183, 207-212, 228-233, 395-400, 441-446, and 493-498 of SEQ ID NO:2, a potential amidation site at about amino acid residues 104-107 of SEQ ID NO:2, a potential leucine zipper motif at about amino acid residues 112-133 of SEQ ID NO:2, and potential sugar transport protein signature 1 domain at about amino acid residues 97-114 of SEQ ID NO:2.

[0428] A MEMSAT analysis of the polypeptide sequence of SEQ ID NO:2 was also performed, predicting thirteen transmembrane domains in the amino acid sequence of human 8099 (SEQ ID NO:2) at about residues 32-49, 58-74, 81-101, 109-130, 138-156, 165-184, 198-217, 279-301, 315-338, 346-364, 463-487, 499-521, and 529-549. Further analysis of the amino acid sequence of SEQ ID NO:2 (e.g., alignment with, for example, known E. coli sugar symporter proteins and a known human facilitative glucose transporter protein) showed that the second transmembrane domain at about amino acid residues 58-74 of SEQ ID NO:2 is not utilized, resulting in the presence of twelve transmembrane domains in the amino acid sequence of human 8099 (SEQ ID NO:2).

[0429] A search of the amino acid sequence of human 8099 was also performed against the ProDom database resulting in the identification of several transmembrane domains, a glycosyltransferase domain, and a sugar transport domain in the amino acid sequence of SEQ ID NO:2.

[0430] The human 8099 amino acid sequence was aligned with the amino acid sequence of the galactose-proton symporter GALP from E. coli using the CLUSTAL W (1.74) multiple sequence alignment program. The results of the alignment are set forth in FIG. 4. The human 8099 amino acid sequence was also aligned with the amino acid sequence of the arabinose-proton symporter ARAE from E. coli using the CLUSTAL W (1.74) multiple sequence alignment program. The results of the alignment are set forth in FIG. 5. The human 8099 amino acid sequence was also aligned with the amino acid sequence of the facilitative glucose transporter GLUT8 from Homo sapiens using the CLUSTAL W (1.74) multiple sequence alignment program. The results of the alignment are set forth in FIG. 7. Based on its homology to GLUT8, 8099 is also referred to herein as “GLUT8 homologue” or “GLUT8h” and can be used interchangeably throughout.

[0431] A search using the polypeptide sequence of human 46455 (SEQ ID NO:5) was performed against the HMM database in PFAM (FIGS. 10A-C) resulting in the identification of a sugar transporter family domain in the amino acid sequence of human 46455 at about residues 58-469 of SEQ ID NO:5 (score=−63.4), a potential sodium:galactoside symporter family domain in the amino acid sequence of human 46455 at about residues 212-505 of SEQ ID NO:5 (score=−121.2), and a potential monocarboxylate transporter domain in the amino acid sequence of human 46455 at about residues 60-473 of SEQ ID NO:5 (score=−208.2).

[0432] The amino acid sequence of human 46455 was analyzed using the program PSORT to predict the localization of the proteins within the cell. This program assesses the presence of different targeting and localization amino acid sequences within the query sequence. The results of this analysis show that human 46455 may be localized to the endoplasmic reticulum, mitochondria, nucleus or secretory vesicles.

[0433] Searches of the amino acid sequence of human 46455 were further performed against the Prosite database. These searches resulted in the identification in the amino acid sequence of human 46455 of a potential N-glycosylation site at about amino acid residues 199-202 of SEQ ID NO:5, a potential cAMP- and cGMP-dependent protein kinase C phosphorylation site at about amino acid residues 414-417 of SEQ ID NO:5, a number of potential protein kinase C phosphorylation sites at about amino acid residues 344-346, 413-415, 442-444, and 518-520 of SEQ ID NO:5, a number of potential casein kinase II phosphorylation sites at about amino acid residues 11-14, 943-946, 959-962, 983-986, 1074-1077, 1108-1111, and 1112-1115 of SEQ ID NO:5, a number of potential N-myristoylation sites at about amino acid residues 89-94, 106-111, 288-293, 679-684, 767-772, 847-852, and 933-938 of SEQ ID NO:5, an amidation site at about amino acid residues 223-226 of SEQ ID NO:5, and an ATP/GTP-binding site motif A (P-loop) at about amino acid residues 1008-1015 of SEQ ID NO:5.

[0434] A MEMSAT analysis of the polypeptide sequence of SEQ ID NO:5 was also performed, predicting eleven transmembrane domains in the amino acid sequence of human 46455 (SEQ ID NO:5) at about residues 98-118, 126-145, 165-181, 188-205, 218-238, 273-294, 323-341, 357-377, 386-410, 423-441, and 462-485. Further analysis of the amino acid sequence of SEQ ID NO:5 (e.g., analysis of the hydropathy plot set forth in FIG. 9) resulted in the identification of a twelfth transmembrane domain at about amino acid residues 58-74 of SEQ ID NO:5.

[0435] A search of the amino acid sequence of human 46455 was also performed against the ProDom database resulting in the identification of a transmembrane efflux domain in the amino acid sequence of SEQ ID NO:5.

[0436] The human 46455 amino acid sequence was aligned with the amino acid sequence of Z92825 from C. elegans using the CLUSTAL W (1.74) multiple sequence alignment program. The results of the alignment are set forth in FIG. 11.

[0437] Isolation of the Human 54414 and 53763 cDNA

[0438] The invention is based, at least in part, on the discovery of genes encoding novel members of the potassium channel family. The entire sequence of human clone Fbh54414 was determined and found to contain an open reading frame termed human “54414”. The entire sequence of human clone Fbh53763 was determined and found to contain an open reading frame termed human “53763”.

[0439] The nucleotide sequence encoding the human 54414 is shown in FIGS. 12A-D and is set forth as SEQ ID NO:7. The protein encoded by this nucleic acid comprises about 1118 amino acids and has the amino acid sequence shown in FIGS. 12A-D and set forth as SEQ ID NO:8. The coding region (open reading frame) of SEQ ID NO:7 is set forth as SEQ ID NO:9. Clone Fbh54414, comprising the coding region of human 54414, was deposited with the American Type Culture Collection (ATCC®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0440] The nucleotide sequence encoding the human 53763 is shown in FIGS. 16A-C and is set forth as SEQ ID NO:10. The protein encoded by this nucleic acid comprises about 638 amino acids and has the amino acid sequence shown in FIGS. 16A-C and set forth as SEQ ID NO:11. The coding region (open reading frame) of SEQ ID NO:10 is set forth as SEQ ID NO:12. Clone Fbh53763, comprising the coding region of human 53763, was deposited with the American Type Culture Collection (ATCC®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0441] Analysis of the Human 54414 and 53763 Molecules

[0442] The amino acid sequences of human 54414 was analyzed using the program PSORT to predict the localization of the proteins within the cell. The results of the analyses show that human 54414 may be localized to the endoplasmic reticulum, the nucleus, secretory vesicles, or the mitochondria.

[0443] Analysis of the amino acid sequences of human 54414 was performed using MEMSAT. The amino acid sequence of human 54414 was also compared to the amino acid sequences of known potassium transporters (FIGS. 15A-B). This analysis resulted in the identification of six possible transmembrane domains in the amino acid sequence of human 54414 at residues 64-83, 104-127, 135-153, 161-173, 199-217, and 257-274 of SEQ ID NO:8 (FIG. 13).

[0444] Searches of the amino acid sequences of human 54414 were performed against the HMM database (FIG. 14). These searches resulted in the identification of an “ion transport protein domain”, at about residues 104-277 of SEQ ID NO:8 (score=62.4).

[0445] Searches of the amino acid sequence of human 54414 were further performed against the Prosite™ database. These searches resulted in the identification of several possible N-glycosylation sites at about amino acids residues 66-69, 99-102, 290-293, 545-548, 554-557, 573-576, 981-984, and 1106-1109 of SEQ ID NO:8, several possible cAMP- and cGMP-dependent protein kinase phosphorylation sites at about amino acids residues 625-628, 994-997, 1002-1005, and 1100-1103 of SEQ ID NO:8, several possible protein kinase C phosphorylation sites at about amino acid residues 43-45, 59-61, 68-70, 126-128, 158-160, 254-256, 298-300, 308-310, 354-356, 385-387, 464-466, 605-607, 903-905, 939-941, 947-949, 1005-1007, 1012-1014, 1030-1032, and 1099-1101 of SEQ ID NO:8, several possible casein kinase II phosphorylation sites at about amino acid residues 43-46, 115-118, 338-341, 386-389, 393-396, 485-488, 556-559, 651-654, 655-658, 663-666, 784-787, 837-840, 867-870, 907-910, 926-929, 943-946, 959-962, 983-986, 1074-1077, 1108-1111, and 1112 -1115 of SEQ ID NO:8, several possible N-myristoylation sites at about amino acid residues 89-94, 106-111, 288-293, 679-684, 767-772, 847-852, and 933-938 of SEQ ID NO:8, a possible amidation site at about amino acid residues 223-226 of SEQ ID NO:8, and a possible ATP/GTP-binding site motif A (P-loop) at about amino acid residues 1008-1015 of SEQ ID NO:8.

[0446] The amino acid sequence of human 53763 was analyzed using the program PSORT to predict the localization of the proteins within the cell. The results of the analyses further show that human 53763 may be localized to the endoplasmic reticulum, the mitochondria, or the nucleus.

[0447] Analysis of the amino acid sequences of human 53763 was performed using MEMSAT. The amino acid sequence of human 53763 was also compared to the amino acid sequences of known potassium transporters (FIG. 19). This analysis resulted in the identification of six possible transmembrane domains in the amino acid sequence of human 53763 at residues 230-248, 287-303, 314-335, 346-368, 382-402, and 451-473 of SEQ ID NO:11 (FIG. 17).

[0448] Searches of the amino acid sequence of human 53763 were also performed against the HMM database (FIGS. 18A-B). These searches resulted in the identification of a “NADH-ubiquinone/plastoquinone oxidoreductase domain” at about residues 317-467 of SEQ ID NO:11 (score=-81.7), an “ion transport protein domain” at about residues 281-472 of SEQ ID NO:11 (score=116.9), and a “K⁺ channel tetramerisation domain” at about residues 8-156 of SEQ IDNO:11 (score=156.7).

[0449] Searches of the amino acid sequence of human 53763 were also performed against the Prosite™ database. These searches resulted in the identification in the amino acid sequence of human 53763 a number of potential N-glycosylation sites at amino acid residues 84-84, 259-262, 266-269, 518-521, and 536-539 of SEQ ID NO:11, a potential cAMP- and cGMP-dependent protein kinase phosphorylation site at amino acid residues 561-564 of SEQ ID NO:11, protein kinase C phosphorylation sites at amino acid residues 21-23, 25-27, 86-88, 120-122, 155-157, 205-207, 224-226, 336-338, 374-376, and 564-566 of SEQ ID NO:11, casein kinase II phosphorylation sites at amino acid residues 17-20, 49-52, 146-149, 283-286, 378-381, 414-417, 520-523, 541-544, 546-549, 553-556, 564-567, and 579-582 of SEQ ID NO:11, and N-myristoylation sites at amino acid residues 31-36, 76-81, 83-88, 89-94, 142-147, 176-181, 191-196, 199-204, 407-412, 450-455, 477-482, 590-595, and 606-611 of SEQ ID NO:11.

[0450] Searches of the amino acid sequences of human 54414 and human 53763 were also performed against the ProDom database. A potassium ionic calcium activated domain and two potassium ionic subunits were identified in the amino acid sequence of 54414 (SEQ ID NO:8). Several transmembrane domains and transport family domains were identified in the the amino acid sequence of 53763 (SEQ ID NO:11).

[0451] The amino acid sequences of human 54414 and human 53763 were further analyzed for the presence of a “pore domain”, also known as a “P-region domain”. A pore domain was identified in the amino acid sequence of human 54414 at about residues 229-250 of SEQ ID NO:8. A pore domain was identified in the amino acid sequence of human 53763 at about residues 426-441 of SEQ ID NO:11.

[0452] The amino acid sequences of human 54414 and human 53763 were also analyzed for the presence of a “potassium channel signature sequence motif” (see Joiner, W. J. et al. (1998) Nat. Neurosci. 1:462-469 and references cited therein). A potassium channel signature sequence motif was identified in the amino acid sequence of human 54414 at about residues 239-246 of SEQ ID NO:8. A potassium channel signature sequence motif was identified in the amino acid sequence of human 53763 at about residues 436-441 of SEQ ID NO:11.

[0453] The amino acid sequence of human 53763 was also analyzed for the presence of a “voltage sensor motif”. A voltage sensor motif was identified in the amino acid sequence of human 53763 at about residues 348-363 of SEQ ID NO:11. Positively charged amino acid residues in the voltage sensor motif were identified about residues 348, 351, 354, 357, 360, and 363 of SEQ ID NO:5.

[0454] Isolation of the Human 67076, 67102, 44181, 67084FL, or 67084alt cDNAs

[0455] The invention is based, at least in part, on the discovery of a human gene encoding novel polypeptides, referred to herein as human 67076, 67102, 44181, 67084FL, and 67084alt. The entire sequence of the human clone 67076 was determined and found to contain an open reading frame termed human “67076.” The nucleotide sequence of the human 67076 gene is set forth in FIGS. 20A-E and in the Sequence Listing as SEQ ID NO:13. The amino acid sequence of the human 67076 expression product is set forth in FIGS. 20A-E and in the Sequence Listing as SEQ ID NO:14. The 67076 polypeptide comprises 1129 amino acids. The coding region (open reading frame) of SEQ ID NO:13 is set forth as SEQ ID NO:15. Clone 67076, comprising the coding region of human 67076, was deposited with the American Type Culture Collection (ATCC®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0456] The entire sequence of the human clone 67102 as determined and found to contain an open reading frame termed human “67102.” The nucleotide sequence of the human gene is set forth in FIGS. 24A-E and in the Sequence Listing as SEQ ID NO:16. The amino acid sequence of the human 67102 expression product is set forth in FIGS. 24A-E and in the Sequence Listing as SEQ ID NO:17. The 67102 polypeptide comprises 1426 amino acids. The coding region (open reading frame) of SEQ ID NO:16 is set forth as SEQ ID NO:18. Clone 67102, comprising the coding region of human 67102, was deposited with the American Type Culture Collection (ATCC(®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0457] The entire sequence of the human clone 44181 was determined and found to contain an open reading frame termed human “44181.” The nucleotide sequence of the human 44181 gene is set forth in FIGS. 28A-E and in the Sequence Listing as SEQ ID NO:19. The amino acid sequence of the human 44181 expression product is set forth in FIGS. 7A-E and in the Sequence Listing as SEQ ID NO:20. The 44181 polypeptide comprises 1177 amino acids. The coding region (open reading frame) of SEQ ID NO:19 is set forth as SEQ ID NO:21. Clone 44181, comprising the coding region of human 44181, was deposited with the American Type Culture Collection (ATCC(®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0458] The entire sequence of the human clone 67084FL was determined and found to contain an open reading frame termed human “67084FL.” The nucleotide sequence of the human 67084FL gene is set forth in FIGS. 32A-D and in the Sequence Listing as SEQ ID NO:22. The amino acid sequence of the human 67084FL expression product is set forth in FIGS. 32A-D and in the Sequence Listing as SEQ ID NO:23. The 67084FL polypeptide comprises 1084 amino acids. The coding region (open reading frame) of SEQ ID NO:22 is set forth as SEQ ID NO:24. Clone 67084FL, comprising the coding region of human 67084FL, was deposited with the American Type Culture Collection (ATCC®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0459] The entire sequence of the human clone 67084alt was determined and found to contain an open reading frame termed human “67084alt.” The nucleotide sequence of the human 67084alt gene is set forth in FIGS. 36A-D and in the Sequence Listing as SEQ ID NO:25. The amino acid sequence of the human 67084alt expression product is set forth in FIGS. 36A-D and in the Sequence Listing as SEQ ID NO:26. The 67084alt polypeptide comprises 1095 amino acids. The coding region (open reading frame) of SEQ ID NO:25 is set forth as SEQ ID NO:27. Clone 67084alt, comprising the coding region of human 67084alt, was deposited with the American Type Culture Collection (ATCC®), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______, and assigned Accession No. ______.

[0460] Analysis of the Human 67076, 67102, 44181, 67084FL, or 67084alt Molecules

[0461] The amino acid sequences of human 67076, 67102, 44181, 67084FL, or 67084alt were analyzed for the presence of sequence motifs specific for P-type ATPases (as defined in Tang, X. et al. (1996) Science 272:1495-1497 and Fagan, M. J. and Saier, M. H. (1994) J. Mol. Evol. 38:57).

[0462] These analyses resulted in the identification of a P-type ATPase sequence I motif in the amino acid sequence of human 67076 at residues 173-181 of SEQ ID NO:14, in the amino acid sequence of human 67102 at residues 208-216 of SEQ ID NO:17, in the amino acid sequence of human 44181 at residues 173-181 of SEQ ID NO:20, in the amino acid sequence of human 67084FL at residues 213-221 of SEQ ID NO:23, and in the amino acid sequence of human 67084alt at residues 213-221 of SEQ ID NO:26.

[0463] These analyses also resulted in the identification of a P-type ATPase sequence 2 motif in the amino acid sequence of human 67076 at residues 406-415 of SEQ ID NO:14, in the amino acid sequence of human 67102 at residues 435-444 of SEQ ID NO:17, in the amino acid sequence of human 44181 at residues 404-413 of SEQ ID NO:20, in the amino acid sequence of human 67084FL at residues 413-422 of SEQ ID NO:23, and in the amino acid sequence of human 67084alt at residues 413-422 of SEQ ID NO:26.

[0464] These analyses further resulted in the identification of a P-type ATPase sequence 3 motif in the amino acid sequence of human 67076 at residues 813-824 of SEQ ID NO:14, in the amino acid sequence of human 67102 at residues 1054-1064 of SEQ ID NO:17, in the amino acid sequence of human 44181 at residues 819-829 of SEQ ID NO:20, in the amino acid sequence of human 67084FL at residues 820-830 of SEQ ID NO:23, and in the amino acid sequence of human 67084alt at residues 820-830 of SEQ ID NO:26.

[0465] The amino acid sequences of human 67076, 67102, 44181, 67084FL, and 67084alt were also analyzed for the presence of phospholipid transporter specific amino acid residues (as defined in Tang, X. et al. (1996) Science 272:1495-1497). These analyses also resulted in the identification of phospholipid transporter specific amino acid residues in the amino acid sequence of human 67076 at residues 174, 177, 407, 813, 823, and 824 of SEQ ID NO:14. These analyses resulted in the identification of phospholipid transporter specific amino acid residues 208, 209, 212, 436, 1054, 1063, and 1064 in the amino acid sequence of human 67102 at residues of SEQ ID NO:17. These analyses further resulted in the identification of phospholipid transporter specific amino acid residues 174, 177, 405, 819, 928, and 929 in the amino acid sequence of human 44181 at residues of SEQ ID NO:20. These analyses further resulted in the identification of phospholipid transporter specific amino acid residues 214, 217, 820, 829, and 830 in the amino acid sequence of human 67084FL at residues of SEQ ID NO:23. These analyses still further resulted in the identification of phospholipid transporter specific amino acid residues 214, 217, 820, 829, and 830 in the amino acid sequence of human 67084alt at residues of SEQ ID NO:26.

[0466] The amino acid sequences of human 67076, 67102, 44181, 67084FL, and 67084alt were also analyzed for the presence of extramembrane domains. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 67076 at residues 105-291 of SEQ ID NO:14. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 67076 at residues 366-872 of SEQ ID NO:14. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 67102 at residues 141-321 of SEQ ID NO:17. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 67102 at residues 391-581 of SEQ ID NO:17. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 44181 at residues 105-289 of SEQ ID NO:20. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 44181 at residues 364-877 of SEQ ID NO:20. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 67084FL at residues 145-330 of SEQ ID NO:23. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 67084FL at residues 380-886 of SEQ ID NO:23. An N-terminal large extramembrane domain was identified in the amino acid sequence of human 67084alt at residues 145-330 of SEQ ID NO:26. A C-terminal large extramembrane domain was identified in the amino acid sequence of human 67084alt at residues 380-886 of SEQ ID NO:26.

[0467] The amino acid sequence of human 67076 was analyzed using the program PSORT to predict the localization of the proteins within the cell. This program assesses the presence of different targeting and localization amino acid sequences within the query sequence. The results of this analysis predict that human 67076 may be localized to the endoplasmic reticulum.

[0468] Searches of the amino acid sequence of human 67076 were further performed against the Prosite database. These searches resulted in the identification in the amino acid sequence of human 67076 of a number of potential N-glycosylation sites at amino acid residues121-124, 392-395, 761-764, 992-995, and 1098-1101 of SEQ ID NO:14, a number of potential cAMP-and cGMP-dependent protein kinase phosphorylation sites at amino acid residues135-138, 545-548, 1091-1094, and 1102-1105 of SEQ ID NO:14, a number of potential protein kinase C phosphorylation sites at amino acid residues 47-49, 138-140, 204-206, 250-252, 254-256, 278-280, 308-310, 328-330, 334-336, 408-410, 680-682, 701-703, 708-710, 733-735, 736-738, 1008-1010, 1094-1096, 1100-1102, 1109-1111, and 1113-1115 of SEQ ID NO:14, a number of casein kinase II phosphorylation sites at amino acid residues 30-33, 264-267, 282-285, 328-331, 413-416, 442-445, 449-452, 494-497, 646-649, 693-696, 704-707, 762-765, 813-816, 924-927, 982-985, and 1121-1124 of SEQ ID NO:14, a number of potential tyrosine kinase phosphorylation sites at amino acid residues 252-258, 739-747 of SEQ ID NO:14, a number of N-myristoylation sites at amino acid residues 388-393, 440-445,482-487,514-519, 564-569,753-758, and 807-812 of SEQ IDNO:14, an ATP/GTP-binding site motif (P-loop) at amino acid residues 271-278 of SEQ ID NO:14, and an E1-E2 ATPases phosphorylation site at amino acid residues 409-415 of SEQ ID NO:14.

[0469] A MEMSAT analysis of the polypeptide sequence of SEQ ID NO:14 was also performed, predicting three potential transmembrane domains in the amino acid sequence of human 67076 (SEQ ID NO:14). However, a structural, hydrophobicity, and antigenicity analysis (FIG. 21) resulted in the identification of ten transmembrane domains. Accordingly, the 67076 protein of SEQ ID NO:14 is predicted to have at least ten transmembrane domains, identified as transmembrane (T_(M)) domains 1 through 10, at about residues 57-77, 84-105, 292-313, 345-365, 863-883, 905-926, 956-977, 989-1009, 1021-1041, and 1060-1087.

[0470] A search using the polypeptide sequence of SEQ ID NO:14 was performed against the HMM database in PFAM resulting in the identification of a potential hydrolase domain in the amino acid sequence of human 67076 at about residues 403-837 of SEQ ID NO:14 (score=12.7).

[0471] A search of the amino acid sequence of human 67076 was also performed against the ProDom database resulting in the identification of several hydrolase domains and phosphorylation domains in the amino acid sequence of 67076 (SEQ ID NO:14).

[0472] The amino acid sequence of human 67102 was analyzed using the program PSORT. The results of this analysis predict that human 67102 may be localized to the endoplasmic reticulum.

[0473] Searches of the amino acid sequence of human 67102 were further performed against the Prosite database. These searches resulted in the identification in the amino acid sequence of human 67102 of a number of potential N-glycosylation sites at amino acid residues 29-32, 303-306, 1365-1368, and 1397-1400 of SEQ ID NO:17, a glycosaminoglycan attachment site at amino acid residues 526-529 of SEQ ID NO:17, a number of potential cAMP- and cGMP-dependent protein kinase phosphorylation sites at amino acid residues 38-41, 451-545, 635-638, and 777-780 of SEQ ID NO:17, a number of protein kinase C phosphorylation sites at amino acid residues 47-49, 78-80, 161-163, 240-242, 262-264, 280-282, 437-439, 500-502, 563-565, 633-635, 644-646, 695-697, 743-745, 774-776,827-829, 1000-1002, 1360-1362, and 1371-1373 of SEQ ID NO:17, a number of potential casein kinase II phosphorylation sites at amino acid residues 20-23, 161-164, 176-179, 184-187, 199-202, 210-213, 232-235, 241-244, 262-265, 312-315, 345-348, 405-408, 442-445, 471-474, 477-480, 543-546, 621-624, 644-647, 670-673, 693-696, 727-730, 850-853, 866-869, 892-895, 977-980, 1074-1077, 1141-1144, 1199-1202, 1221-1224, 1339-1342, 1399-1402, and 1403-1406 of SEQ ID NO:17, two tyrosine kinase phosphorylation sites at amino acid residues 21-28 and 847-854 of SEQ ID NO:17, a number of potential N-myristoylation sites at amino acid residues 69-74, 341-346, 488-493, 510-515, 519-524, 525-530, 651-656, 703-708, 714-719, 901-906, 955-960, 992-997, 1070-1075, 1139-1144, 1229-1234, and 1261-1266 of SEQ ID NO:17, two potential amidation sites at amino acid residues 36-39 and 1371-1374 of SEQ ID NO:17, two ATP/GTP-binding site motif A (P-loop) at amino acid residues 996-1003 and 1364-1371, an E1-E2 ATPases phosphorylation site at amino acid residues 438-444 of SEQ ID NO:17, and a prokaryotic membrane lipoprotein lipid attachment site at amino acid residues 26-36 of SEQ ID NO:17.

[0474] A MEMSAT analysis of the polypeptide sequence of SEQ ID NO:17 was also performed, predicting ten potential transmembrane domains in the amino acid sequence of human 67102 (SEQ ID NO:17) at about residues 98-115, 122-140, 322-344, 366-390, 582-601, 752-770, 1145-1166, 1225-1246, 1253-1276, and 1298-1317.

[0475] A search using the polypeptide sequence of SEQ ID NO:17 was performed against the HMM database in PFAM resulting in the identification of a potential hydrolase domain in the amino acid sequence of human 67102 at about residues 432-1077 of SEQ ID NO:17 (score=1.5), and the identification of a potential DUF6 domain in the amino acid sequence of human 67102 at about residues 1127-1271 of SEQ ID NO:17 (score =-24.6).

[0476] A search of the amino acid sequence of human 67102 was also performed against the ProDom database resulting in the identification of several hydrolase domains and phosphorylation domains in the amino acid sequence of 667102 (SEQ ID NO:17).

[0477] The amino acid sequence of human 44181 was analyzed using the program PSORT. The results of this analysis predict that human 44181 may be localized to the endoplasmic reticulum.

[0478] Searches of the amino acid sequence of human 44181 were further performed against the Prosite database. These searches resulted in the identification in the amino acid sequence of human 44181 of a number of potential N-glycosylation sites at amino acid residues 331-334, 390-393, 449-452, 461-464, 477-480, 786-789, and 998-1001 of SEQ ID NO:20, a number of potential cAMP- and cGMP-dependent protein kinase phosphorylation sites at amino acid residues 577-580, 633-636, and 750-753 of SEQ ID NO:20, a number of protein kinase C phosphorylation sites at amino acid residues 46-48, 163-165, 276-278, 332-334, 406-408, 470-472, 574-576, 636-638, 957-959, 1014-1016, and 1102-1104 of SEQ ID NO:20, a number of potential casein kinase C phosphorylation sites at amino acid residues 115-118, 262-265, 280-283, 411-414, 473-476, 520-523, 527-530, 636-639, 678-681, 737-740, 906-909, 929-932, 1100-1103, 1154-1157, and 1170-1173 of SEQ ID NO:20, a potential tyrosine kinase phosphorylation site at amino acid residues 316-322 of SEQ ID NO:20, a number of potential N-myristoylation sites at amino acid residues 131-136, 596-601, 766-771, and 993-998 of SEQ ID NO:20, and an E1-E2 ATPases phosphorylation site at amino acid residues 407-413 of SEQ ID NO:20.

[0479] A MEMSAT analysis of the polypeptide sequence of SEQ ID NO:20 was also performed, predicting three potential transmembrane domains in the amino acid sequence of human 44181 (SEQ ID NO:20). However, a structural, hydrophobicity, and antigenicity analysis (FIG. 29) resulted in the identification of ten transmembrane domains. Accordingly, the 44181 protein (SEQ ID NO:20) is predicted to have at least ten transmembrane domains, which are identified as transmembrane (T_(M)) domains 1 through 10, at about residues 56-72, 87-103, 290-311, 343-363, 878-898, 911-931, 961-982, 995-1015, 1027-1047, and 1062-1086.

[0480] A search using the polypeptide sequence of SEQ ID NO:20 was performed against the HMM database in PFAM resulting in the identification of a potential E1-E2 ATPase domain in the amino acid sequence of human 44181 at about residues 126-164 of SEQ ID NO:20 (score=8.6), the identification of a potential DUF132 domain in the amino acid sequence of human 44181 at about residues 579-719 of SEQ ID NO:20 (score=−72.9), and the identification of a potential hydrolase domain in the amino acid sequence of human 44181 at about residues 401-842 of SEQ ID NO:20 (score =42.8).

[0481] A search of the amino acid sequence of human 44181 was also performed against the ProDom database A search of the amino acid sequence of human 44181 was also performed against the ProDom database resulting in the identification of several hydrolase domains and phosphorylation domains in the amino acid sequence of 44181 (SEQ ID NO:20).

[0482] A Clustal W (1.74) alignment of the amino acid sequence of human 44181 (SEQ ID NO:20) and human potential phospholipid-transporting ATPase IR (ATIR; GenBank Accession No.:Q9Y2G3) revealed some sequence homology between 44181 and Accession No.:Q9Y2G3.

[0483] The amino acid sequence of human 67084FL was analyzed using the program PSORT. The results of this analysis predict that human 67084FL may be localized to the endoplasmic reticulum.

[0484] Searches of the amino acid sequence of human 67084FL were further performed against the Prosite database. These searches resulted in the identification in the amino acid sequence of human 67084FL of a number of potential N-glycosylation sites at amino acid residues 310-313, 464-467, and 529-532 of SEQ ID NO:23, a potential cAMP- and cGMP-dependent protein kinase phosphorylation site at amino acid residues 1071-1074 of SEQ ID NO:23, a number of protein kinase C phosphorylation sites 82-84, 168-170, 204-206, 301-303, 371-373, 415-417, 486-488, 585-587, 666-668, 744-746, 800-802, 813-815, 872-874, 957-959, and 1009-1011 of SEQ ID NO:23, a number of potential casein kinase II phosphorylation sites at amio acid residues 265-268, 301-304, 402-405, 422-425, 535-538, 596-599, 661-664, 686-689, and 745-748 of SEQ ID NO:23, a tyrosine kinase phosphorylation site at amino acid residues 813-816 of SEQ ID NO:23, a number of potential N-myristoylation sites at amino acid residues 292-297, 462-467, 568-573, 606-611, 824-829, 887-892, and 1026-1031 of SEQ ID NO:23, a potential amidation site at amino acid residues 813-816 of SEQ ID NO:23, a prokaryotic membrane lipoprotein lipid attachment site at amino acid residues 105-115, a leucine zipper pattern at amino acid residues 325-346, and an E1-E2 ATPases phosphorylation site at amino acid residues 416-422 of SEQ ID NO:23.

[0485] A MEMSAT analysis of the polypeptide sequence of SEQ ID NO:23 was also performed, predicting nine potential transmembrane domains in the amino acid sequence of human 67084FL (SEQ ID NO:23). However, a structural, hydrophobicity, and antigenicity analysis (FIG. 33) resulted in the identification of ten transmembrane domains. Accordingly, the 67084FL protein of SEQ ID NO:23 is predicted to have at least ten transmembrane domains, which are identified as transmembrane (T_(M)) domains 1 through 10, at about residues 104-120, 124-144, 331-350, 357-374, 887-903, 912-931, 961-983, 990-1008, 1015-1035, and 1043-1067.

[0486] A search using the polypeptide sequence of SEQ ID NO:23 was performed against the HMM database in PFAM resulting in the identification of two potential E1 -E2 ATPase in the amino acid sequence of human 67084FL at about residues 171-199 of SEQ ID NO:23 (score=3.0) and 277-305 of SEQ ID NO:23 (score=13.0), and a hydrolase domain at about residues 410-843 of of SEQ ID NO:23 (score=19.2).

[0487] A search of the amino acid sequence of human 67084FL was also performed against the ProDom database resulting in the identification of several hydrolase domains, phosphorylation domains, and ATPase domains in the amino acid sequence of 67084FL (SEQ ID NO:23).

[0488] A Clustal W (1.74) alignment of the amino acid sequence of human 67084FL (SEQ ID NO:23) and human membrane transport protein (MTRP-1; GenBank Accession No.:Y71056, International Publicaiton No. WO 2000/26245-A2) revealed some sequence homology between 67084FL and Accession No.: Y71056.

[0489] The amino acid sequence of human 67084alt was analyzed using the program PSORT. The results of this analysis predict that human 67084alt may be localized to the endoplasmic reticulum.

[0490] Searches of the amino acid sequence of human 67084alt were further performed against the Prosite database. These searches resulted in the identification in the amino acid sequence of human 67084alt of a number of potential N-glycosylation sites at amino acid residues 310-313, 464-467, and 529-532 of SEQ ID NO:26, a potential cAMP- and cGMP-dependent protein kinase phosphorylation site at amino acid residues 1083-1086, a number of protein kinase C phosphorylation sites at amino acid residues 82-84, 168-170, 204-2-6, 301-303, 371-373, 415-417, 486-488, 585-587, 666-668, 744-746, 800-802, 813-815, 872-874, 957-959, and 1009-1011 of SEQ ID NO:26, a number of potential casein kinase II phosphorylation sites at amino acid residues 265-268, 301-304, 402-405, 422-445, 535-538, 596-599, 661-664, 686-689, and 745-748 of SEQ ID NO:26, a tyrosine kinase phosphorylation site at amino acid residues 641-648, a number of potential N-myristoylation sites at amino acid residues 292-297, 462-467, 568-573, 606-611, 824-829, 887-892, and 1026-1031 of SEQ ID NO:26, a potential amidation site at amino acid residues 813-816 of SEQ ID NO:26, a potential prokaryotic membrane lipoprotein lipid attachment site at amino acid residues 105-115 of SEQ ID NO:26, a leucine zipper pattern at amino acid residues 325-346 of SEQ ID NO:26, and an E1-E2 ATPases phosphorylation site at amino acid residues 416-422 of SEQ ID NO:26.

[0491] A MEMSAT analysis of the polypeptide sequence of SEQ ID NO:26 was also performed, predicting nine potential transmembrane domains in the amino acid sequence of human 67084alt (SEQ ID NO:26). However, a structural, hydrophobicity, and antigenicity analysis (FIG. 37) resulted in the identification of ten transmembrane domains. Accordingly, the 67084alt protein of SEQ ID NO:26 is predicted to have at least ten transmembrane domains, which are identified as transmembrane (T_(M)) domains 1 through 10, at about residues 104-120, 124-144, 331-350, 357-374, 887-903, 912-931, 961-983, 990-1008, 1015-1035, and 1043-1067.

[0492] A search using the polypeptide sequence of SEQ ID NO:26 was performed against the HMM database in PFAM resulting in the identification of two potential E1 -E2 ATPase in the amino acid sequence of human 67084alt at about residues 42-70 of SEQ ID NO:26 (score=3.0) and 105-133 of SEQ ID NO:26 (score=13.0), and a potential hydrolase domain at about amino acid residues 410-843 of SEQ ID NO:26 (score=19.2).

[0493] A search of the amino acid sequence of human 67084alt was also performed against the ProDom database resulting in the identification of several hydrolase domains, phosphorylation domains, and ATPase domains in the amino acid sequence of 67084alt (SEQ ID NO:26).

[0494] A Clustal W (1.74) alignment of the amino acid sequence of human 67084alt (SEQ ID NO:14) and human membrane transport protein (MTRP-1; GenBank Accession No.:Y71056, International Publicaiton No. WO 2000/26245-A2) revealed some sequence homology between 67084alt and Accession No.: Y71056.

Example 2 Tissue Expression of Human 8099,46455,54414,53763,

[0495]67076, 67102, 44181, Full Length 67084 (67084FL), and 67084alt mRNA

[0496] Tissue Distribution of Human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, and 67084alt mRNA Using Tagman™ Analysis

[0497] This example describes the tissue distribution of human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt mRNA in a variety of cells and tissues, as determined using the TaqMan™ procedure. The Taqman™ procedure is a quantitative, reverse transcription PCR-based approach for detecting mRNA. The RT-PCR reaction exploits the 5′ nuclease activity of AmpliTaq Gold™ DNA Polymerase to cleave a TaqMan™ probe during PCR. Briefly, cDNA was generated from the samples of interest, e.g., lung, ovary, colon, and breast normal and tumor samples, and used as the starting material for PCR amplification. In addition to the 5′ and 3′ gene-specific primers, a gene-specific oligonucleotide probe (complementary to the region being amplified) was included in the reaction (i.e., the Taqman™ probe). The TaqMan™ probe includes the oligonucleotide with a fluorescent reporter dye covalently linked to the 5′ end of the probe (such as FAM (6-carboxyfluorescein), TET (6-carboxy-4,7,2′,7′-tetrachlorofluorescein), JOE (6-carboxy-4,5-dichloro-2,7-dimethoxyfluorescein), or VIC) and a quencher dye (TAMRA (6-carboxy-N,N,N′,N′-tetramethylrhodamine) at the 3′ end of the probe.

[0498] During the PCR reaction, cleavage of the probe separates the reporter dye and the quencher dye, resulting in increased fluorescence of the reporter. Accumulation of PCR products is detected directly by monitoring the increase in fluorescence of the reporter dye.

[0499] When the probe is intact, the proximity of the reporter dye to the quencher dye results in suppression of the reporter fluorescence. During PCR, if the target of interest is present, the probe specifically anneals between the forward and reverse primer sites. The 5′-3′ nucleolytic activity of the AmpliTaq™ Gold DNA Polymerase cleaves the probe between the reporter and the quencher only if the probe hybridizes to the target. The probe fragments are then displaced from the target, and polymerization of the strand continues. The 3′ end of the probe is blocked to prevent extension of the probe during PCR. This process occurs in every cycle and does not interfere with the exponential accumulation of product. RNA was prepared using the trizol method and treated with DNase to remove contaminating genomic DNA. cDNA was synthesized using standard techniques. Mock cDNA synthesis in the absence of reverse transcriptase resulted in samples with no detectable PCR amplification of the control gene confirms efficient removal of genomic DNA contamination.

[0500] Tissue Distribution of Human 8099

[0501] A human tissue panel was tested revealing highest expression of human 8099 mRNA in congestive heart failure (CHF) heart, normal prostate, and brain (see Table 1, below). TABLE 1 β 2 Tissue Type Mean Mean ∂∂ Ct Expression Artery normal 30.83 22.31 8.52 2.7241 Aorta diseased 32.77 22.32 10.45 0.7149 Vein normal 29.41 20.23 9.18 1.724 Coronary SMC 31.2 20.91 10.3 0.7932 HUVEC 32.16 21.38 10.78 0.5687 Hemangioma 32.86 19.66 13.21 0.1059 Heart normal 28.05 20.43 7.62 5.0834 Heart CHF 26.98 20.68 6.3 12.6914 Kidney 27.76 20.45 7.3 6.3238 Skeletal Muscle 29.7 22.17 7.53 5.4294 Adipose normal 34.16 20.59 13.56 0.0828 Pancreas 33.23 22.29 10.94 0.5108 primary osteoblasts 32 20.61 11.39 0.3726 Osteoclasts (diff) 30.9 17.55 13.35 0.0958 Skin normal 34.12 22.45 11.68 0.3058 Spinal cord normal 31.93 21.07 10.87 0.5362 Brain Cortex normal 28.4 22.34 6.06 14.9885 Brain Hypothalamus normal 29.68 22.35 7.34 6.1936 Nerve 32.96 22.25 10.72 0.5949 DRG (Dorsal Root Ganglion) 30.81 22.15 8.65 2.4808 Breast normal 31.91 21.14 10.77 0.5747 Breast tumor 32.73 20.93 11.81 0.2785 Ovary normal 30.41 19.82 10.6 0.6465 Ovary Tumor 28.36 19.06 9.31 1.5755 Prostate Normal 27.29 19.77 7.52 5.4482

[0502] Tissue Distribution of Human 46455

[0503] A human vessel and tissue panel was tested revealing highest expression of human 46455 mRNA in human umbilical vein endothelial cells (HUVEC), erythroid cells, normal artery, megakaryocytes, kidney, and CHF heart. 46455 was expressed at higher levels in lung tumor, breast tumor, and colon tumor versus normal lung, breast and colon tissues, indicating a possible role for 46455 in cellular proliferation disorders (see Table 2, below). TABLE 2 β 2 Tissue Type Mean Mean ∂∂ Ct Expression Artery normal 28.05 24.09 2.67 157.6722 Aorta diseased 28.75 23.66 3.79 72.0429 Vein normal 27.75 21.72 4.75 37.1627 Coronary SMC 28.2 25.12 1.78 290.176 HUVEC 24.18 22.59 0.29 817.9021 Hemangioma 25.15 20.98 2.88 135.8419 Heart normal 26.44 21.82 3.33 99.4421 Heart CHF 25.54 21.09 3.15 112.6563 Kidney 25.98 21.49 3.2 108.8188 Skeletal Muscle 28.22 24.14 2.79 144.586 Adipose normal 28.38 22.21 4.88 33.9605 Pancreas 27.91 23.22 3.4 94.4045 primary osteoblasts 27.11 21.85 3.97 63.8133 Osteoclasts (diff) 23.64 18.8 3.55 85.3775 Skin normal 28.43 23.27 3.88 68.1567 Spinal cord normal 26.88 22.12 3.47 90.2456 Brain Cortex normal 26.42 23.4 1.73 301.452 Brain Hypothalamus normal 28.1 23.55 3.26 104.386 Nerve 28.59 23.88 3.43 92.7827 DRG (Dorsal Root Ganglion) 28.33 23.76 3.28 102.9489 Breast normal 27.31 22.32 3.7 76.9465 Breast tumor 26.47 22.11 3.07 119.0797 Ovary normal 26.59 22.16 3.13 113.8337 Ovary Tumor 28.47 21.84 5.33 24.8605 Prostate Normal 27.09 21.68 4.12 57.5117 Prostate Tumor 26.51 21.58 3.64 80.2141 Salivary glands 27.16 20.81 5.07 29.8733 Colon normal 26.3 20 5 31.1419 Colon Tumor 25.09 20.52 3.29 102.5927 Lung normal 26.02 19.75 4.98 31.6862 Lung tumor 25.09 21.31 2.48 178.6243 Lung COPD 25.26 19.71 4.26 52.193 Colon IBD 26.3 18.91 6.1 14.5786 Liver normal 27.66 21.8 4.57 42.101 Liver fibrosis 29.31 24.09 3.92 65.8351 Spleen normal 27.41 21.41 4.71 38.2075 Tonsil normal 25.23 19.32 4.63 40.5262 Lymph node normal 26.15 20.35 4.51 43.8889 Small intestine normal 28.23 21.73 5.22 26.8302 Skin-Decubitus 27.18 22.82 3.06 119.908 Synovium 28 21.12 5.59 20.6889 BM-MNC 26.13 19.32 5.51 21.9445 Activated PBMC 25.2 17.95 5.96 16.12 Neutrophils 24.45 19.5 3.65 79.66 Megakaryocytes 22.5 18.95 2.26 208.772 Erythroid 24.2 21.69 1.23 427.7975

[0504] Tissue Distribution of Human 53763

[0505] A human vessel and tissue panel was tested revealing highest expression of human 53763 mRNA in normal brain cortex, normal hypothalamus, prostate tumor, normal prostate, dorsal root ganglion, and normal breast tissue (see Table 3, below). TABLE 3 β 2 Tissue Type Mean Mean ∂∂ Ct Expression Artery normal 40 22.41 16.07 0 Aorta diseased 40 22.05 16.44 0 Vein normal 40 19.75 18.74 0 Coronary SMC 35.16 21.86 11.79 0 HUVEC 40 20.41 18.08 0 Hemangioma 40 18.52 19.96 0 Heart normal 39.43 19.55 18.37 0 Heart CHF 40 18.98 19.5 0 Kidney 39.44 19.76 18.16 0 Skeletal Muscle 38.97 21.57 15.89 0 Adipose normal 40 20.09 18.4 0 Pancreas 38.91 20.84 16.56 0 primary osteoblasts 40 19.87 18.61 0 Osteoclasts (diff) 40 17.09 21.4 0 Skin normal 39.59 21.22 16.86 0 Spinal cord normal 31.72 20.14 10.07 0.9303 Brain Cortex normal 23.07 21.56 0.01 996.5403 Brain Hypothalamus normal 26.15 20.98 3.65 79.3844 Nerve 39.08 21.23 16.33 0 DRG (Dorsal Root Ganglion) 31.66 21.3 8.86 2.1596 Breast normal 27.25 20.41 5.33 24.9468 Breast tumor 40 20.02 18.46 0 Ovary normal 40 19.66 18.83 0 Ovary Tumor 40 19.7 18.79 0 Prostate Normal 29.68 19.32 8.85 2.1671 Prostate Tumor 28.14 19.95 6.67 9.8204 Salivary glands 40 18.97 19.52 0 Colon normal 39.09 17.8 19.78 0 Colon Tumor 40 18.63 19.86 0 Lung normal 40 17.49 21 0 Lung tumor 39.66 19.81 18.34 0 Lung COPD 40 17.97 20.52 0 Colon IBD 40 17.3 21.18 0 Liver normal 40 19.57 18.91 0 Liver fibrosis 40 21.34 17.15 0 Spleen normal 40 19.27 19.22 0 Tonsil normal 33.5 16.75 15.24 0.0258 Lymph node normal 38.61 18.4 18.7 0 Small intestine normal 36.56 19.96 15.08 0 Skin-Decubitus 39.43 20.41 17.51 0 Synovium 40 19.32 19.16 0 BM-MNC 40 18.21 20.27 0 Activated PBMC 38.88 17.5 19.88 0 Neutrophils 40 18.38 20.11 0 Megakaryocytes 40 18.09 20.39 0 Erythroid 40 21.23 17.25 0

[0506] Tissue Distribution of Human 67076

[0507] A human vessel panel was tested revealing highest expression of human 67076 mRNA in normal aorta, diseased artery, and static HUVEC (see Table 4, below). TABLE 4 β 2 Ex- Tissue Type Mean Mean ∂∂ Ct pression Aortic SMC 25.58 21.16 4.42 46.8762 Coronary SMC 29.11 24.36 4.76 36.906 Huvec Static 23.55 20.59 2.96 128.0696 Huvec LSS 23.41 20.06 3.35 98.073 H/Adipose/MET 8 27.7 20.51 7.18 6.8723 H/Artery/Normal/Carotid/CLN 595 26.82 19.34 7.48 5.6014 H/Artery/Normal/Carotid/CLN 598 28.79 20.41 8.37 3.0226 H/Artery/normal/NDR 352 29.41 21.68 7.73 4.7102 H/IM Artery/Normal/AMC 73 32.65 23.77 8.88 2.1152 H/Muscular Artery/Normal/AMC 236 29.2 23.34 5.87 17.1577 H/Muscular Artery/Normal/AMC 254/ 29.68 22.56 7.13 7.1393 H/Muscular Artery/Normal/AMC 259 29.63 22.25 7.37 6.0452 H/Muscular Artery/Normal/AMC 261 30.12 22.67 7.45 5.7191 H/Muscular Artery/Normal/AMC 275 30.2 24.2 6 15.6792 H/Aorta/Diseased/PIT 732 30.73 22.36 8.38 3.0121 H/Aorta/Diseased/PIT 710 29.6 23.14 6.46 11.3199 H/Aorta/Diseased/PIT 711 29.35 22.63 6.72 9.4531 H/Aorta/Diseased/PIT 712 28.77 22.02 6.75 9.2585 H/Artery/Diseased/iliac/NDR 753 26.11 19.41 6.71 9.585 H/Artery/Diseased/Tibial/PIT 679 29.82 20.34 9.47 1.4101 H/Vein/Normal/SaphenousAMC 107 31.66 21.07 10.59 0.6488 H/Vein/Normal/NDR 239 33.13 21.65 11.49 0.3477 H/Vein/Normal/Saphenous/NDR 237 29.71 20.59 9.12 1.7972 H/Vein/Normal/PIT 1010 28.34 22.05 6.3 12.6914 H/Vein/Normal/AMC 191 28.64 22.15 6.49 11.164 H/Vein/Normal/AMC 130 27.41 21.27 6.14 14.1309 H/Vein/Normal/AMC 188 30.56 24.09 6.46 11.3199 H/Vein/Normal/AMC 196 29.89 20.93 8.96 2.008 H/Vein/Normal/AMC 211 32.55 23.52 9.03 1.9196 H/Vein/Normal/AMC 214 30.93 22.99 7.95 4.058 M/Artery/Diseased/CAR 1174 24.56 23.05 1.5 352.3302 M/Artery/Diseased/CAR 1175 24.98 19.89 5.09 29.2585 M/Aorta/Normal/PRI 286 25.52 18.68 6.84 8.7288 M/Artery/Normal/PRI 324 25.13 20.65 4.48 44.8111 M/Aorta/Normal/PRI 264 24.14 24.74 −0.6 1515.7166 M/Artery/Normal/PRI 320 24.93 20.29 4.64 40.1071 M/Vein/Normal/PRI 328 26.67 20.04 6.63 10.0965 HUVEC Vehicle 26.64 21 5.63 20.1232 HUVEC Mev 25.54 20.3 5.25 26.3692 HAEC Vehicle 25.7 20.66 5.04 30.2903 HAEC Mev 27.84 22.41 5.43 23.1957

[0508] Tissue Distribution of Human 67102

[0509] A human tissue panel was tested revealing highest expression of human 67102 mRNA in normal kidney tissue and diseased artery (see Table 5, below). TABLE 5 β 2 Ex- Tissue Type Mean Mean ∂∂ Ct pression Aortic SMC 28.34 21.88 6.47 11.2807 Coronary SMC 29.98 23.11 6.88 8.5196 Huvec Static 27.55 21.41 6.14 14.18 Huvec LSS 27.72 21.12 6.59 10.3444 H/Adipose/MET 8 30.56 20.57 9.99 0.9834 H/Artery/Normal/Carotid/CLN 595 31.42 20.3 11.13 0.4478 H/Artery/Normal/Carotid/CLN 598 32.23 21.69 10.54 0.6717 H/Artery/normal/NDR 352 31.34 22.44 8.9 2.0933 H/IM Artery/Normal/AMC 73 33.46 23.98 9.48 1.4003 H/Muscular Artery/Normal/AMC 236 30.48 23.52 6.96 8.0321 H/Muscular Artery/Normal/AMC 247 33.9 24.07 9.82 1.1025 H/Muscular Artery/Normal/AMC 254/ 31.12 23.43 7.68 4.8594 H/Muscular Artery/Normal/AMC 259 30.47 23.07 7.4 5.9208 H/Muscular Artery/Normal/AMC 261 31.32 22.92 8.4 2.9501 H/Muscular Artery/Normal/AMC 275 31.31 24.78 6.53 10.8212 H/Aorta/Diseased/PIT 732 31.73 22.76 8.97 1.9942 H/Aorta/Diseased/PIT 710 30.33 23.36 6.97 7.9767 H/Aorta/Diseased/PIT 711 31.02 23.3 7.72 4.7265 H/Aorta/Diseased/PIT 712 30.57 22.71 7.86 4.3043 H/Artery/Diseased/iliac/NDR 753 27.22 20.07 7.15 7.041 H/Artery/Diseased/Tibial/PIT 679 32 21.19 10.81 0.557 H/Vein/Normal/SaphenousAMC 107 31.57 22.08 9.49 1.3859 H/Vein/Normal/NDR 239 33.44 22.16 11.28 0.4021 H/Vein/Normal/Saphenous/NDR 237 31.32 21.01 10.31 0.7877 H/Vein/Normal/PIT 1010 29.86 22.36 7.5 5.5243 H/Vein/Normal/AMC 191 30.36 22.53 7.84 4.3796 H/Vein/Normal/AMC 130 30.08 22.32 7.75 4.6293 H/Vein/Normal/AMC 188 32.93 25.01 7.92 4.129 H/Vein/Normal/AMC 196 32.24 21.61 10.64 0.6288 H/Vein/Normal/AMC 211 36.16 23.51 12.65 0 H/Vein/Normal/AMC 214 35.59 24 11.6 0 M/Artery/Diseased/CAR 1175 29.73 21.84 7.89 4.2011 M/Aorta/Normal/543 34.84 29.17 5.67 19.6408 M/Artery/Diseased/CAR 1174 31.11 26.59 4.52 43.5857 M/Pancreas/PRI 2 32.48 26.33 6.15 14.082 M/Kidney/Normal/MPI 88 30.23 26.84 3.38 96.0547 M/Kidney/Normal/MPI 282 29.34 25.94 3.4 95.0612 HUVEC Vehicle 29.25 21.45 7.8 4.4871 HUVEC Mev 28.16 20.87 7.29 6.3899 HAEC Vehicle 28.14 21.16 6.97 7.9491 HAEC Mev 29.61 22.66 6.95 8.088

[0510] In addition, a human vessel panel was tested, which revealed high expression of human 67102 mRNA in normal artery, HUVEC, coronary smooth muscle cells, diseased aorta, and normal hypothalamus (see Table, 6, below). TABLE 6 β 2 Tissue Type Mean Mean ∂∂ Ct Expression Artery normal 27.32 21.75 5.57 21.0505 Aorta diseased 28.27 21.71 6.55 10.6353 Vein normal 30.38 19.83 10.55 0.6693 Coronary SMC 28.61 22.23 6.38 12.0485 HUVEC 26.32 20.32 6 15.5709 Hemangioma 25.91 19.07 6.83 8.7895 Heart normal 27.16 19.98 7.17 6.9441 Heart CHF 27.2 19.06 8.14 3.545 Kidney 25.54 19.59 5.96 16.12 Skeletal Muscle 30.52 21.5 9.03 1.9196 Adipose normal 30.11 19.95 10.15 0.8771 Pancreas 29.57 21.23 8.33 3.1076 primary osteoblasts 28.09 19.85 8.23 3.3191 Osteoclasts (diff) 29.79 17.02 12.77 0.1432 Skin normal 29.31 21.41 7.89 4.2011 Spinal cord normal 28.3 20.36 7.93 4.0863 Brain Cortex normal 28.25 22.04 6.21 13.5084 Brain Hypothalamus normal 28.93 21.49 7.44 5.7589 Nerve 28.34 21.3 7.04 7.5989 DRG (Dorsal Root Ganglion) 29.16 21.11 8.04 3.7994 Breast normal 27.81 20.47 7.34 6.1508 Breast tumor 29.08 20.41 8.68 2.4466 Ovary normal 26.44 19.7 6.74 9.3878 Ovary Tumor 30.93 19.6 11.34 0.3871 Prostate Normal 28.11 19.48 8.63 2.5241 Prostate Tumor 27.68 19.68 8 3.9063 Salivary glands 28.9 19.18 9.71 1.194 Colon Tumor 27.98 18.82 9.16 1.742 Lung normal 26.96 17.4 9.56 1.3202 Lung tumor 27.82 19.64 8.19 3.4361 Lung COPD 26.38 17.66 8.72 2.3633 Colon IBD 28.27 17.29 10.98 0.4934 Liver normal 29.14 19.58 9.56 1.3248 Liver fibrosis 29.89 21.08 8.8 2.2358 Spleen normal 26.95 19.09 7.86 4.3193 Tonsil normal 25.01 16.8 8.21 3.3654 Lymph node normal 26.3 18.22 8.09 3.6828 Small intestine normal 29.03 19.59 9.45 1.4347 Skin-Decubitus 27.66 20.32 7.34 6.1722 Synovium 28.22 19.23 8.98 1.9804 BM-MNC 29.57 18.46 11.12 0.4509 Activated PBMC 28.38 17.25 11.14 0.4447 Neutrophils 27.43 18.4 9.04 1.8997 Megakaryocytes 26.72 17.88 8.84 2.1822 Erythroid 31.52 21.26 10.26 0.8183 Colon normal 30.07 19.25 10.82 0.5551

[0511] Tissue Distribution of Human 44181

[0512] A human vessel panel was tested revealing highest expression of human 44181 mRNA in LSS HUVEC (see Table 7, below). TABLE 7 β 2 Tissue Type Mean Mean ∂∂ Ct Expression Static Huvec 25.37 19.18 6.19 13.697 LSS Huvec 25.7 20.02 5.68 19.4377 Aortic SMC 28.75 20.32 8.43 2.9095 Coronary SMC 28.52 21.2 7.31 6.3019 H/Adipose/MET 9 36.07 18.41 17.66 0 Diseased Heart/PIT 1 29.28 21.15 8.13 3.5697 H/Artery/Normal/Carotid/CLN 37.9 18.32 19.59 0 595 H/Artery/Normal/Carotid/CLN 39.97 19.49 20.48 0 598 H/Artery/normal/NDR 352 40 20.2 19.8 0 H/Artery/Normal/AMC 150 40 22.27 17.73 0 H/Artery/Normal/AMC 73 40 23.84 16.16 0 IMA/AMC 247 39.73 22.79 16.95 0 IMA/AMC 254 33.79 22.23 11.56 0.3324 IMA/AMC 259 33.68 21.12 12.56 0.1656 IMA/AMC 261 34.73 21.23 13.5 0.0863 IMA/AMC 275 40 24.52 15.48 0 IMA/AMC 279 30.89 22.41 8.48 0 H/Artery/Diseased/iliac/NDR 36.59 18.43 18.16 0 753 H/Artery/Diseased/Tibial/PIT 40 19.84 20.16 0 679 Aorta/Diseased/PIT 732 34.74 21.32 13.41 0.0916 Aorta/Diseased/PIT 710 33.04 22.48 10.56 0.6624 Aorta/Diseased/PIT 711 31.89 22.09 9.8 1.1218 Aorta/Diseased/PIT 712 32.92 22.09 10.84 0.5474 H/Vein/Normal/Saphenous/N 32.66 16.82 15.83 0.0172 DR 721 H/Vein/Normal/SaphenousA 40 20 20 0 MC 107 H/Vein/Normal/NDR 239 40 20.61 19.39 0 H/Vein/Normal/Saphenous/N 40 19.1 20.9 0 DR 237 H/Vein/Normal/NDR 235 40 21.34 18.66 0 H/Vein/Normal/MPI 1101 33.56 19.59 13.98 0.0621 HMVEC/Vehicle/24 hr 30.04 17.84 12.2 0.2125 HMVEC/Mev/24hr/1X 29.77 18 11.76 0.2883 HMVEC/MEV/24HR/2.5X 30.32 18.67 11.65 0.3112 HMVEC/MEV/48HR/1X 31.58 18.8 12.79 0.1417 HMVEC/MEV/48HR/2.5X 31.77 18.37 13.4 0.0922 HUVEC/Vehicle/24 hr 30.5 18.15 12.36 0.1909 HUVEC/Mev/24hr/1X 30.28 17.52 12.76 0.1442 HUVEC/MEV/24HR/2.5X 29.35 19.18 10.18 0.865 HUVEC/MEV/48HR/1X 35.68 21.54 14.14 0 HUVEC/MEV/48HR/2.5X 34.7 23 11.7 0.3016

[0513] Tissue Distribution of Human 67084

[0514] A human vessel panel was tested revealing highest expression of human 67084 mRNA in HUVEC, LSS HUVEC, and coronary smooth muscle cells (see Table 8, below). TABLE 8 β 2 Ex- Tissue Type Mean Mean ∂∂ Ct pression Aortic SMC 25.92 19.23 6.7 9.6517 Coronary SMC 26.59 20.36 6.23 13.3224 Huvec Static 23.39 18.5 4.88 33.843 Huvec LSS 24.31 18.32 5.99 15.7883 H/Adipose/MET 9 26.4 18.46 7.94 4.0721 H/Artery/Normal/Carotid/CLN 595 26.83 18.84 8 3.9198 H/Artery/Normal/Carotid/CLN 598 28.49 20.16 8.34 3.0968 H/Artery/normal/NDR 352 27.12 20.32 6.8 8.9432 H/IM Artery/Normal/AMC 73 31.48 23.36 8.12 3.607 H/Muscular Artery/Normal/AMC 236 30.93 23.56 7.38 6.0243 H/Muscular Artery/Normal/AMC 247 33.77 24.84 8.92 2.0645 H/Muscular Artery/Normal/AMC 254/ 30.69 23.68 7 7.7855 H/Muscular Artery/Normal/AMC 259 29.9 22.12 7.78 4.5497 H/Muscular Artery/Normal/AMC 261 29.93 21.13 8.8 2.2436 H/Muscular Artery/Normal/AMC 275 30.29 22.97 7.33 6.2367 H/Aorta/Diseased/PIT 732 29.02 21.35 7.67 4.8932 H/Aorta/Diseased/PIT 710 31.36 22.8 8.56 2.6496 H/Aorta/Diseased/PIT 711 31.31 22.6 8.71 2.3963 H/Aorta/Diseased/PIT 712 31.4 22.48 8.92 2.0645 H/Artery/Diseased/iliac/NDR 753 25.37 17.73 7.64 4.996 H/Artery/Diseased/Tibial/PIT 679 28.55 19.45 9.11 1.816 H/Vein/Normal/SaphenousAMC 107 29.48 21.11 8.38 3.0121 H/Vein/Normal/Saphenous/NDR 237 28.67 19.86 8.8 2.2358 H/Vein/Normal/PIT 1010 28.31 20.55 7.76 4.5973 H/Vein/Normal/AMC 191 29.25 20.77 8.47 2.8104 H/Vein/Normal/AMC 130 28.32 20.45 7.88 4.2598 H/Vein/Normal/AMC 188 31.68 24.61 7.06 7.4943 H/Vein/Normal/NDR 239 35.65 29.23 6.42 0 HUVEC Vehicle 26.86 20.14 6.71 9.5188 HUVEC Mev 25.83 18.52 7.3 6.3238 HAEC Vehicle 26.57 19.64 6.94 8.1443 HAEC Mev 27.81 21.13 6.67 9.7864

Example 3 Expression of Recombinant 67076,67102,44181,

[0515]67084FL, or 67084alt Polypeptide in Bacterial Cells

[0516] In this example, human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt is expressed as a recombinant glutathione-S-transferase (GST) fusion polypeptide in E. coli and the fusion polypeptide is isolated and characterized. Specifically, 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt is fused to GST and this fusion polypeptide is expressed in E. coli, e.g., strain PEB 199. Expression of the GST-PLTR fusion polypeptide in PEB 199 is induced with IPTG. The recombinant fusion polypeptide is purified from crude bacterial lysates of the induced PEB 199 strain by affinity chromatography on glutathione beads. Using polyacrylamide gel electrophoretic analysis of the polypeptide purified from the bacterial lysates, the molecular weight of the resultant fusion polypeptide is determined.

Example 4 Expression of Recombinant 8099,46455,54414,

[0517]53763, 67076, 67102, 44181, 67084FL, or 67084alt Polypeptides in COS Cells

[0518] To express the human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene in COS cells, the pcDNA/Amp vector by Invitrogen Corporation (San Diego, Calif.) is used. This vector contains an SV40 origin of replication, an ampicillin resistance gene, an E. coli replication origin, a CMV promoter followed by a polylinker region, and an SV40 intron and polyadenylation site. A DNA fragment encoding the entire PLTR polypeptide and an HA tag (Wilson et al. (1984) Cell 37:767) or a FLAG tag fused in-frame to its 3′ end of the fragment is cloned into the polylinker region of the vector, thereby placing the expression of the recombinant polypeptide under the control of the CMV promoter.

[0519] To construct the plasmid, the human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt DNA sequence is amplified by PCR using two primers. The 5′ primer contains the restriction site of interest followed by approximately twenty nucleotides of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt coding sequence starting from the initiation codon; the 3′ end sequence contains complementary sequences to the other restriction site of interest, a translation stop codon, the HA tag or FLAG tag and the last 20 nucleotides of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt coding sequence. The PCR amplified fragment and the pCDNA/Amp vector are digested with the appropriate restriction enzymes and the vector is dephosphorylated using the CIAP enzyme (New England Biolabs, Beverly, Mass.). Preferably the two restriction sites chosen are different so that the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt gene is inserted in the correct orientation. The ligation mixture is transformed into E. coli cells (strains HB101, DH5α, SURE, available from Stratagene Cloning Systems, La Jolla, Calif., can be used), the transformed culture is plated on ampicillin media plates, and resistant colonies are selected. Plasmid DNA is isolated from transformants and examined by restriction analysis for the presence of the correct fragment.

[0520] COS cells are subsequently transfected with the human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-pcDNA/Amp plasmid DNA using the calcium phosphate or calcium chloride co-precipitation methods, DEAE-dextran-mediated transfection, lipofection, or electroporation. Other suitable methods for transfecting host cells can be found in Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989. The expression of the IC54420 polypeptide is detected by radiolabelling (³⁵S-methionine or ³⁵S-cysteine available from NEN, Boston, MA, can be used) and immunoprecipitation (Harlow, E. and Lane, D. Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1988) using an HA specific monoclonal antibody. Briefly, the cells are labeled for 8 hours with ³⁵S-methionine (or ³⁵S-cysteine). The culture media are then collected and the cells are lysed using detergents (RIPA buffer, 150 mM NaCl, 1% NP-40, 0.1% SDS, 0.5% DOC, 50 mM Tris, pH 7.5). Both the cell lysate and the culture media are precipitated with an HA specific monoclonal antibody. Precipitated polypeptides are then analyzed by SDS-PAGE.

[0521] Alternatively, DNA containing the human 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt coding sequence is cloned directly into the polylinker of the pCDNA/Amp vector using the appropriate restriction sites. The resulting plasmid is transfected into COS cells in the manner described above, and the expression of the 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt polypeptide is detected by radiolabelling and immunoprecipitation using a 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt-specific monoclonal antibody.

[0522] Equivalents

[0523] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

0 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 40 <210> SEQ ID NO 1 <211> LENGTH: 2725 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (180)...(2033) <400> SEQUENCE: 1 ccacgcgtcc ggccttccga aatagaaaca aagttggtca caaatcacat tagctttgcc 60 cgaagttttt ccccacactc ttctttagca tgctattatg gggaaagtga ccactcctgg 120 gagcgggggt ggtcggggcg gtttggtggc ggggaagcgg ctgtaacttc tacgtgacc 179 atg gta cct gtt gaa aac acc gag ggc ccc agt ctg ctg aac cag aag 227 Met Val Pro Val Glu Asn Thr Glu Gly Pro Ser Leu Leu Asn Gln Lys 1 5 10 15 ggg aca gcc gtg gag acg gag ggc agc ggc agc cgg cat cct ccc tgg 275 Gly Thr Ala Val Glu Thr Glu Gly Ser Gly Ser Arg His Pro Pro Trp 20 25 30 gcg aga ggc tgc ggc atg ttt acc ttc ctg tca tct gtc act gct gct 323 Ala Arg Gly Cys Gly Met Phe Thr Phe Leu Ser Ser Val Thr Ala Ala 35 40 45 gtc agt ggc ctc ctg gtg ggt tat gaa ctt ggg atc atc tct ggg gct 371 Val Ser Gly Leu Leu Val Gly Tyr Glu Leu Gly Ile Ile Ser Gly Ala 50 55 60 ctt ctt cag atc aaa acc tta tta gcc ctg agc tgc cat gag cag gaa 419 Leu Leu Gln Ile Lys Thr Leu Leu Ala Leu Ser Cys His Glu Gln Glu 65 70 75 80 atg gtt gtg agc tcc ctc gtc att gga gcc ctc ctt gcc tca ctc acc 467 Met Val Val Ser Ser Leu Val Ile Gly Ala Leu Leu Ala Ser Leu Thr 85 90 95 gga ggg gtc ctg ata gac aga tat gga aga agg aca gca atc atc ttg 515 Gly Gly Val Leu Ile Asp Arg Tyr Gly Arg Arg Thr Ala Ile Ile Leu 100 105 110 tca tcc tgc ctg ctt gga ctc gga agc tta gtc ttg atc ctc agt tta 563 Ser Ser Cys Leu Leu Gly Leu Gly Ser Leu Val Leu Ile Leu Ser Leu 115 120 125 tcc tac acg gtt ctt ata gtg gga cgc att gcc ata ggg gtc tcc atc 611 Ser Tyr Thr Val Leu Ile Val Gly Arg Ile Ala Ile Gly Val Ser Ile 130 135 140 tcc ctc tct tcc att gcc act tgt gtt tac atc gca gag att gct cct 659 Ser Leu Ser Ser Ile Ala Thr Cys Val Tyr Ile Ala Glu Ile Ala Pro 145 150 155 160 caa cac aga aga ggc ctt ctt gtg tca ctg aat gag ctg atg att gtc 707 Gln His Arg Arg Gly Leu Leu Val Ser Leu Asn Glu Leu Met Ile Val 165 170 175 atc ggc att ctt tct gcc tat att tca aat tac gca ttt gcc aat gtt 755 Ile Gly Ile Leu Ser Ala Tyr Ile Ser Asn Tyr Ala Phe Ala Asn Val 180 185 190 ttc cat ggc tgg aag tac atg ttt ggt ctt gtg att ccc ttg gga gtt 803 Phe His Gly Trp Lys Tyr Met Phe Gly Leu Val Ile Pro Leu Gly Val 195 200 205 ttg caa gca att gca atg tat ttt ctt cct cca agc cct cgg ttt ctg 851 Leu Gln Ala Ile Ala Met Tyr Phe Leu Pro Pro Ser Pro Arg Phe Leu 210 215 220 gtg atg aaa gga caa gag gga gct gct agc aag gtt ctt gga agg tta 899 Val Met Lys Gly Gln Glu Gly Ala Ala Ser Lys Val Leu Gly Arg Leu 225 230 235 240 aga gca ctc tca gat aca act gag gaa ctc act gtg atc aaa tcc tcc 947 Arg Ala Leu Ser Asp Thr Thr Glu Glu Leu Thr Val Ile Lys Ser Ser 245 250 255 ctg aaa gat gaa tat cag tac agt ttt tgg gat ctg ttt cgt tca aaa 995 Leu Lys Asp Glu Tyr Gln Tyr Ser Phe Trp Asp Leu Phe Arg Ser Lys 260 265 270 gac aac atg cgg acc cga ata atg ata gga cta aca cta gta ttt ttt 1043 Asp Asn Met Arg Thr Arg Ile Met Ile Gly Leu Thr Leu Val Phe Phe 275 280 285 gta caa atc act ggc caa cca aac ata ttg ttc tat gca tca act gtt 1091 Val Gln Ile Thr Gly Gln Pro Asn Ile Leu Phe Tyr Ala Ser Thr Val 290 295 300 ttg aag tca gtt gga ttt caa agc aat gag gca gct agc ctc gcc tcc 1139 Leu Lys Ser Val Gly Phe Gln Ser Asn Glu Ala Ala Ser Leu Ala Ser 305 310 315 320 act ggg gtt gga gtc gtc aag gtc att agc acc atc cct gcc act ctt 1187 Thr Gly Val Gly Val Val Lys Val Ile Ser Thr Ile Pro Ala Thr Leu 325 330 335 ctt gta gac cat gtc ggc agc aaa aca ttc ctc tgc att ggc tcc tct 1235 Leu Val Asp His Val Gly Ser Lys Thr Phe Leu Cys Ile Gly Ser Ser 340 345 350 gtg atg gca gct tcg ttg gtg acc atg ggc atc gta aat ctc aac atc 1283 Val Met Ala Ala Ser Leu Val Thr Met Gly Ile Val Asn Leu Asn Ile 355 360 365 cac atg aac ttc acc cat atc tgc aga agc cac aat tct atc aac cag 1331 His Met Asn Phe Thr His Ile Cys Arg Ser His Asn Ser Ile Asn Gln 370 375 380 tcc ttg gat gag tct gtg att tat gga cca gga aac ctg tca acc aac 1379 Ser Leu Asp Glu Ser Val Ile Tyr Gly Pro Gly Asn Leu Ser Thr Asn 385 390 395 400 aac aat act ctc aga gac cac ttc aaa ggg att tct tcc cat agc aga 1427 Asn Asn Thr Leu Arg Asp His Phe Lys Gly Ile Ser Ser His Ser Arg 405 410 415 agc tca ctc atg ccc ctg aga aat gat gtg gat aag aga ggg gag acg 1475 Ser Ser Leu Met Pro Leu Arg Asn Asp Val Asp Lys Arg Gly Glu Thr 420 425 430 acc tca gca tcc ttg cta aat gct gga tta agc cac act gaa tac cag 1523 Thr Ser Ala Ser Leu Leu Asn Ala Gly Leu Ser His Thr Glu Tyr Gln 435 440 445 ata gtc aca gac cct ggg gac gtc cca gct ttt ttg aaa tgg ctg tcc 1571 Ile Val Thr Asp Pro Gly Asp Val Pro Ala Phe Leu Lys Trp Leu Ser 450 455 460 tta gcc agc ttg ctt gtt tat gtt gct gct ttt tca att ggt cta gga 1619 Leu Ala Ser Leu Leu Val Tyr Val Ala Ala Phe Ser Ile Gly Leu Gly 465 470 475 480 cca atg ccc tgg ctg gtg ctc agc gag atc ttt cct ggt ggg atc aga 1667 Pro Met Pro Trp Leu Val Leu Ser Glu Ile Phe Pro Gly Gly Ile Arg 485 490 495 gga cga gcc atg gct tta act tct agc atg aac tgg ggc atc aat ctc 1715 Gly Arg Ala Met Ala Leu Thr Ser Ser Met Asn Trp Gly Ile Asn Leu 500 505 510 ctc atc tcg ctg aca ttt ttg act gta act gat ctt att ggc ctg cca 1763 Leu Ile Ser Leu Thr Phe Leu Thr Val Thr Asp Leu Ile Gly Leu Pro 515 520 525 tgg gtg tgc ttt ata tat aca atc atg agt cta gca tcc ctg ctt ttt 1811 Trp Val Cys Phe Ile Tyr Thr Ile Met Ser Leu Ala Ser Leu Leu Phe 530 535 540 gtt gtt atg ttt ata cct gag aca aag gga tgc tct ttg gaa caa ata 1859 Val Val Met Phe Ile Pro Glu Thr Lys Gly Cys Ser Leu Glu Gln Ile 545 550 555 560 tca atg gag cta gca aaa gtg aac tat gtg aaa aac aac att tgt ttt 1907 Ser Met Glu Leu Ala Lys Val Asn Tyr Val Lys Asn Asn Ile Cys Phe 565 570 575 atg agt cat cac caa gaa gaa tta gtg cca aaa cag cct caa aaa aga 1955 Met Ser His His Gln Glu Glu Leu Val Pro Lys Gln Pro Gln Lys Arg 580 585 590 aaa ccc cag gag cag ctc ttg gag tgt aac aag ctg tgt ggt agg ggc 2003 Lys Pro Gln Glu Gln Leu Leu Glu Cys Asn Lys Leu Cys Gly Arg Gly 595 600 605 caa tcc agg cag ctt tct cca gag acc taa tggcctcaac accttctgaa 2053 Gln Ser Arg Gln Leu Ser Pro Glu Thr * 610 615 cgtggatagt gccagaacac ttaggagggt gtctttggac caatgcatag ttgcgactcc 2113 tgtgctctct tttcagtgtc atggaactgg ttttgaagag acactctgaa atgataaaga 2173 cagcctttaa tccccctcct ccccagaagg aacctcaaaa ggtagatgag gtacaaggtc 2233 ctaagtgatc tctttttctg agcaggatat caggttaaaa aaaaaaagtt actggctggt 2293 ttaatacttt ctaccttctt cacagagcag cctttgaata gactatgtcc tagtgaagac 2353 atcaacctcc gccttaagct atgtatgtat ggaggccagt cgcagcttta ttatgcagac 2413 acacaagtgg tctggacatg agggtacagt ttctgcctac caagacacta cttgcactgg 2473 atcttacgca aaaaagaacc agaacacaca gtgtggacaa ctgcccatat attctatcta 2533 gattaggaga gggtcctggc taggatttta gtggtaattc ctagttacat tcaacaagta 2593 taaagattat agagcttatt ttatgaacta taaactataa tttaatgcaa aatatccttt 2653 tatgaatttc atgttaatat tgtgaaatat taaaataatt ccgcaataaa aaaaaaaaaa 2713 aagggcggcc gc 2725 <210> SEQ ID NO 2 <211> LENGTH: 617 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 2 Met Val Pro Val Glu Asn Thr Glu Gly Pro Ser Leu Leu Asn Gln Lys 1 5 10 15 Gly Thr Ala Val Glu Thr Glu Gly Ser Gly Ser Arg His Pro Pro Trp 20 25 30 Ala Arg Gly Cys Gly Met Phe Thr Phe Leu Ser Ser Val Thr Ala Ala 35 40 45 Val Ser Gly Leu Leu Val Gly Tyr Glu Leu Gly Ile Ile Ser Gly Ala 50 55 60 Leu Leu Gln Ile Lys Thr Leu Leu Ala Leu Ser Cys His Glu Gln Glu 65 70 75 80 Met Val Val Ser Ser Leu Val Ile Gly Ala Leu Leu Ala Ser Leu Thr 85 90 95 Gly Gly Val Leu Ile Asp Arg Tyr Gly Arg Arg Thr Ala Ile Ile Leu 100 105 110 Ser Ser Cys Leu Leu Gly Leu Gly Ser Leu Val Leu Ile Leu Ser Leu 115 120 125 Ser Tyr Thr Val Leu Ile Val Gly Arg Ile Ala Ile Gly Val Ser Ile 130 135 140 Ser Leu Ser Ser Ile Ala Thr Cys Val Tyr Ile Ala Glu Ile Ala Pro 145 150 155 160 Gln His Arg Arg Gly Leu Leu Val Ser Leu Asn Glu Leu Met Ile Val 165 170 175 Ile Gly Ile Leu Ser Ala Tyr Ile Ser Asn Tyr Ala Phe Ala Asn Val 180 185 190 Phe His Gly Trp Lys Tyr Met Phe Gly Leu Val Ile Pro Leu Gly Val 195 200 205 Leu Gln Ala Ile Ala Met Tyr Phe Leu Pro Pro Ser Pro Arg Phe Leu 210 215 220 Val Met Lys Gly Gln Glu Gly Ala Ala Ser Lys Val Leu Gly Arg Leu 225 230 235 240 Arg Ala Leu Ser Asp Thr Thr Glu Glu Leu Thr Val Ile Lys Ser Ser 245 250 255 Leu Lys Asp Glu Tyr Gln Tyr Ser Phe Trp Asp Leu Phe Arg Ser Lys 260 265 270 Asp Asn Met Arg Thr Arg Ile Met Ile Gly Leu Thr Leu Val Phe Phe 275 280 285 Val Gln Ile Thr Gly Gln Pro Asn Ile Leu Phe Tyr Ala Ser Thr Val 290 295 300 Leu Lys Ser Val Gly Phe Gln Ser Asn Glu Ala Ala Ser Leu Ala Ser 305 310 315 320 Thr Gly Val Gly Val Val Lys Val Ile Ser Thr Ile Pro Ala Thr Leu 325 330 335 Leu Val Asp His Val Gly Ser Lys Thr Phe Leu Cys Ile Gly Ser Ser 340 345 350 Val Met Ala Ala Ser Leu Val Thr Met Gly Ile Val Asn Leu Asn Ile 355 360 365 His Met Asn Phe Thr His Ile Cys Arg Ser His Asn Ser Ile Asn Gln 370 375 380 Ser Leu Asp Glu Ser Val Ile Tyr Gly Pro Gly Asn Leu Ser Thr Asn 385 390 395 400 Asn Asn Thr Leu Arg Asp His Phe Lys Gly Ile Ser Ser His Ser Arg 405 410 415 Ser Ser Leu Met Pro Leu Arg Asn Asp Val Asp Lys Arg Gly Glu Thr 420 425 430 Thr Ser Ala Ser Leu Leu Asn Ala Gly Leu Ser His Thr Glu Tyr Gln 435 440 445 Ile Val Thr Asp Pro Gly Asp Val Pro Ala Phe Leu Lys Trp Leu Ser 450 455 460 Leu Ala Ser Leu Leu Val Tyr Val Ala Ala Phe Ser Ile Gly Leu Gly 465 470 475 480 Pro Met Pro Trp Leu Val Leu Ser Glu Ile Phe Pro Gly Gly Ile Arg 485 490 495 Gly Arg Ala Met Ala Leu Thr Ser Ser Met Asn Trp Gly Ile Asn Leu 500 505 510 Leu Ile Ser Leu Thr Phe Leu Thr Val Thr Asp Leu Ile Gly Leu Pro 515 520 525 Trp Val Cys Phe Ile Tyr Thr Ile Met Ser Leu Ala Ser Leu Leu Phe 530 535 540 Val Val Met Phe Ile Pro Glu Thr Lys Gly Cys Ser Leu Glu Gln Ile 545 550 555 560 Ser Met Glu Leu Ala Lys Val Asn Tyr Val Lys Asn Asn Ile Cys Phe 565 570 575 Met Ser His His Gln Glu Glu Leu Val Pro Lys Gln Pro Gln Lys Arg 580 585 590 Lys Pro Gln Glu Gln Leu Leu Glu Cys Asn Lys Leu Cys Gly Arg Gly 595 600 605 Gln Ser Arg Gln Leu Ser Pro Glu Thr 610 615 <210> SEQ ID NO 3 <211> LENGTH: 1854 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(1854) <400> SEQUENCE: 3 atg gta cct gtt gaa aac acc gag ggc ccc agt ctg ctg aac cag aag 48 Met Val Pro Val Glu Asn Thr Glu Gly Pro Ser Leu Leu Asn Gln Lys 1 5 10 15 ggg aca gcc gtg gag acg gag ggc agc ggc agc cgg cat cct ccc tgg 96 Gly Thr Ala Val Glu Thr Glu Gly Ser Gly Ser Arg His Pro Pro Trp 20 25 30 gcg aga ggc tgc ggc atg ttt acc ttc ctg tca tct gtc act gct gct 144 Ala Arg Gly Cys Gly Met Phe Thr Phe Leu Ser Ser Val Thr Ala Ala 35 40 45 gtc agt ggc ctc ctg gtg ggt tat gaa ctt ggg atc atc tct ggg gct 192 Val Ser Gly Leu Leu Val Gly Tyr Glu Leu Gly Ile Ile Ser Gly Ala 50 55 60 ctt ctt cag atc aaa acc tta tta gcc ctg agc tgc cat gag cag gaa 240 Leu Leu Gln Ile Lys Thr Leu Leu Ala Leu Ser Cys His Glu Gln Glu 65 70 75 80 atg gtt gtg agc tcc ctc gtc att gga gcc ctc ctt gcc tca ctc acc 288 Met Val Val Ser Ser Leu Val Ile Gly Ala Leu Leu Ala Ser Leu Thr 85 90 95 gga ggg gtc ctg ata gac aga tat gga aga agg aca gca atc atc ttg 336 Gly Gly Val Leu Ile Asp Arg Tyr Gly Arg Arg Thr Ala Ile Ile Leu 100 105 110 tca tcc tgc ctg ctt gga ctc gga agc tta gtc ttg atc ctc agt tta 384 Ser Ser Cys Leu Leu Gly Leu Gly Ser Leu Val Leu Ile Leu Ser Leu 115 120 125 tcc tac acg gtt ctt ata gtg gga cgc att gcc ata ggg gtc tcc atc 432 Ser Tyr Thr Val Leu Ile Val Gly Arg Ile Ala Ile Gly Val Ser Ile 130 135 140 tcc ctc tct tcc att gcc act tgt gtt tac atc gca gag att gct cct 480 Ser Leu Ser Ser Ile Ala Thr Cys Val Tyr Ile Ala Glu Ile Ala Pro 145 150 155 160 caa cac aga aga ggc ctt ctt gtg tca ctg aat gag ctg atg att gtc 528 Gln His Arg Arg Gly Leu Leu Val Ser Leu Asn Glu Leu Met Ile Val 165 170 175 atc ggc att ctt tct gcc tat att tca aat tac gca ttt gcc aat gtt 576 Ile Gly Ile Leu Ser Ala Tyr Ile Ser Asn Tyr Ala Phe Ala Asn Val 180 185 190 ttc cat ggc tgg aag tac atg ttt ggt ctt gtg att ccc ttg gga gtt 624 Phe His Gly Trp Lys Tyr Met Phe Gly Leu Val Ile Pro Leu Gly Val 195 200 205 ttg caa gca att gca atg tat ttt ctt cct cca agc cct cgg ttt ctg 672 Leu Gln Ala Ile Ala Met Tyr Phe Leu Pro Pro Ser Pro Arg Phe Leu 210 215 220 gtg atg aaa gga caa gag gga gct gct agc aag gtt ctt gga agg tta 720 Val Met Lys Gly Gln Glu Gly Ala Ala Ser Lys Val Leu Gly Arg Leu 225 230 235 240 aga gca ctc tca gat aca act gag gaa ctc act gtg atc aaa tcc tcc 768 Arg Ala Leu Ser Asp Thr Thr Glu Glu Leu Thr Val Ile Lys Ser Ser 245 250 255 ctg aaa gat gaa tat cag tac agt ttt tgg gat ctg ttt cgt tca aaa 816 Leu Lys Asp Glu Tyr Gln Tyr Ser Phe Trp Asp Leu Phe Arg Ser Lys 260 265 270 gac aac atg cgg acc cga ata atg ata gga cta aca cta gta ttt ttt 864 Asp Asn Met Arg Thr Arg Ile Met Ile Gly Leu Thr Leu Val Phe Phe 275 280 285 gta caa atc act ggc caa cca aac ata ttg ttc tat gca tca act gtt 912 Val Gln Ile Thr Gly Gln Pro Asn Ile Leu Phe Tyr Ala Ser Thr Val 290 295 300 ttg aag tca gtt gga ttt caa agc aat gag gca gct agc ctc gcc tcc 960 Leu Lys Ser Val Gly Phe Gln Ser Asn Glu Ala Ala Ser Leu Ala Ser 305 310 315 320 act ggg gtt gga gtc gtc aag gtc att agc acc atc cct gcc act ctt 1008 Thr Gly Val Gly Val Val Lys Val Ile Ser Thr Ile Pro Ala Thr Leu 325 330 335 ctt gta gac cat gtc ggc agc aaa aca ttc ctc tgc att ggc tcc tct 1056 Leu Val Asp His Val Gly Ser Lys Thr Phe Leu Cys Ile Gly Ser Ser 340 345 350 gtg atg gca gct tcg ttg gtg acc atg ggc atc gta aat ctc aac atc 1104 Val Met Ala Ala Ser Leu Val Thr Met Gly Ile Val Asn Leu Asn Ile 355 360 365 cac atg aac ttc acc cat atc tgc aga agc cac aat tct atc aac cag 1152 His Met Asn Phe Thr His Ile Cys Arg Ser His Asn Ser Ile Asn Gln 370 375 380 tcc ttg gat gag tct gtg att tat gga cca gga aac ctg tca acc aac 1200 Ser Leu Asp Glu Ser Val Ile Tyr Gly Pro Gly Asn Leu Ser Thr Asn 385 390 395 400 aac aat act ctc aga gac cac ttc aaa ggg att tct tcc cat agc aga 1248 Asn Asn Thr Leu Arg Asp His Phe Lys Gly Ile Ser Ser His Ser Arg 405 410 415 agc tca ctc atg ccc ctg aga aat gat gtg gat aag aga ggg gag acg 1296 Ser Ser Leu Met Pro Leu Arg Asn Asp Val Asp Lys Arg Gly Glu Thr 420 425 430 acc tca gca tcc ttg cta aat gct gga tta agc cac act gaa tac cag 1344 Thr Ser Ala Ser Leu Leu Asn Ala Gly Leu Ser His Thr Glu Tyr Gln 435 440 445 ata gtc aca gac cct ggg gac gtc cca gct ttt ttg aaa tgg ctg tcc 1392 Ile Val Thr Asp Pro Gly Asp Val Pro Ala Phe Leu Lys Trp Leu Ser 450 455 460 tta gcc agc ttg ctt gtt tat gtt gct gct ttt tca att ggt cta gga 1440 Leu Ala Ser Leu Leu Val Tyr Val Ala Ala Phe Ser Ile Gly Leu Gly 465 470 475 480 cca atg ccc tgg ctg gtg ctc agc gag atc ttt cct ggt ggg atc aga 1488 Pro Met Pro Trp Leu Val Leu Ser Glu Ile Phe Pro Gly Gly Ile Arg 485 490 495 gga cga gcc atg gct tta act tct agc atg aac tgg ggc atc aat ctc 1536 Gly Arg Ala Met Ala Leu Thr Ser Ser Met Asn Trp Gly Ile Asn Leu 500 505 510 ctc atc tcg ctg aca ttt ttg act gta act gat ctt att ggc ctg cca 1584 Leu Ile Ser Leu Thr Phe Leu Thr Val Thr Asp Leu Ile Gly Leu Pro 515 520 525 tgg gtg tgc ttt ata tat aca atc atg agt cta gca tcc ctg ctt ttt 1632 Trp Val Cys Phe Ile Tyr Thr Ile Met Ser Leu Ala Ser Leu Leu Phe 530 535 540 gtt gtt atg ttt ata cct gag aca aag gga tgc tct ttg gaa caa ata 1680 Val Val Met Phe Ile Pro Glu Thr Lys Gly Cys Ser Leu Glu Gln Ile 545 550 555 560 tca atg gag cta gca aaa gtg aac tat gtg aaa aac aac att tgt ttt 1728 Ser Met Glu Leu Ala Lys Val Asn Tyr Val Lys Asn Asn Ile Cys Phe 565 570 575 atg agt cat cac caa gaa gaa tta gtg cca aaa cag cct caa aaa aga 1776 Met Ser His His Gln Glu Glu Leu Val Pro Lys Gln Pro Gln Lys Arg 580 585 590 aaa ccc cag gag cag ctc ttg gag tgt aac aag ctg tgt ggt agg ggc 1824 Lys Pro Gln Glu Gln Leu Leu Glu Cys Asn Lys Leu Cys Gly Arg Gly 595 600 605 caa tcc agg cag ctt tct cca gag acc taa 1854 Gln Ser Arg Gln Leu Ser Pro Glu Thr * 610 615 <210> SEQ ID NO 4 <211> LENGTH: 2230 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (376)...(1962) <400> SEQUENCE: 4 gtcgacccac gcgtccggca acatggcggc tgccgtggtg cagcgcccgg gctgagcgac 60 agcaagtgca gcgggctcct accccgggtg aggggtggcc tccgcgtggg atcgtgccct 120 cttcagcccg ctcctgtccc cgacatcacg tgtattccgc acgtcccctc cgcgctgtgt 180 gtctactgag acggggaggc gtgacagggc ccgggtccct tctcagtggt gctctgtgct 240 tcagggcaag ctccccgtct ccgggcgcac ttccctcgcc tgtgttcggt ccatcctcct 300 ttctccagcc tcctcccctc gcaggtggga tcgtcggtgg gaccggagcg cgggcgggcg 360 cggccccccg ggacc atg gcc ggg tcc gac acc gcg ccc ttc ctc agc cag 411 Met Ala Gly Ser Asp Thr Ala Pro Phe Leu Ser Gln 1 5 10 gcg gat gac ccg gac gac ggg cca gtg cct ggc acc ccg ggg ttg cca 459 Ala Asp Asp Pro Asp Asp Gly Pro Val Pro Gly Thr Pro Gly Leu Pro 15 20 25 ggg tcc acg ggg aac ccg aag tcc gag gag ccc gag gtc ccg gac cag 507 Gly Ser Thr Gly Asn Pro Lys Ser Glu Glu Pro Glu Val Pro Asp Gln 30 35 40 gag ggg ctg cag cgc atc acc ggc ctg tct ccc ggc cgt tcg gct ctc 555 Glu Gly Leu Gln Arg Ile Thr Gly Leu Ser Pro Gly Arg Ser Ala Leu 45 50 55 60 ata gtg gcg gtg ctg tgc tac atc aat ctc ctg aac tac atg gac cgc 603 Ile Val Ala Val Leu Cys Tyr Ile Asn Leu Leu Asn Tyr Met Asp Arg 65 70 75 ttc acc gtg gct ggc gtc ctt ccc gac atc gag cag ttc ttc aac atc 651 Phe Thr Val Ala Gly Val Leu Pro Asp Ile Glu Gln Phe Phe Asn Ile 80 85 90 ggg gac agt agc tct ggg ctc atc cag acc gtg ttc atc tcc agt tac 699 Gly Asp Ser Ser Ser Gly Leu Ile Gln Thr Val Phe Ile Ser Ser Tyr 95 100 105 atg gtg ttg gca cct gtg ttt ggc tac ctg ggt gac agg tac aat cgg 747 Met Val Leu Ala Pro Val Phe Gly Tyr Leu Gly Asp Arg Tyr Asn Arg 110 115 120 aag tat ctc atg tgc ggg ggc att gcc ttc tgg tcc ctg gtg aca ctg 795 Lys Tyr Leu Met Cys Gly Gly Ile Ala Phe Trp Ser Leu Val Thr Leu 125 130 135 140 ggg tca tcc ttc atc ccc gga gag cat ttc tgg ctg ctc ctc ctg acc 843 Gly Ser Ser Phe Ile Pro Gly Glu His Phe Trp Leu Leu Leu Leu Thr 145 150 155 cgg ggc ctg gtg ggg gtc ggg gag gcc agt tat tcc acc atc gcg ccc 891 Arg Gly Leu Val Gly Val Gly Glu Ala Ser Tyr Ser Thr Ile Ala Pro 160 165 170 act ctc att gcc gac ctc ttt gtg gcc gac cag cgg agc cgg atg ctc 939 Thr Leu Ile Ala Asp Leu Phe Val Ala Asp Gln Arg Ser Arg Met Leu 175 180 185 agc atc ttc tac ttt gcc att ccg gtg ggc agt ggt ctg ggc tac att 987 Ser Ile Phe Tyr Phe Ala Ile Pro Val Gly Ser Gly Leu Gly Tyr Ile 190 195 200 gca ggc tcc aaa gtg aag gat atg gct gga gac tgg cac tgg gct ctg 1035 Ala Gly Ser Lys Val Lys Asp Met Ala Gly Asp Trp His Trp Ala Leu 205 210 215 220 agg gtg aca ccg ggt cta gga gtg gtg gcc gtt ctg ctg ctg ttc ctg 1083 Arg Val Thr Pro Gly Leu Gly Val Val Ala Val Leu Leu Leu Phe Leu 225 230 235 gta gtg cgg gag ccg cca agg gga gcc gtg gag cgc cac tca gat ttg 1131 Val Val Arg Glu Pro Pro Arg Gly Ala Val Glu Arg His Ser Asp Leu 240 245 250 cca ccc ctg aac ccc acc tcg tgg tgg gca gat ctg agg gct ctg gca 1179 Pro Pro Leu Asn Pro Thr Ser Trp Trp Ala Asp Leu Arg Ala Leu Ala 255 260 265 aga aat cct agt ttc gtc ctg tct tcc ctg ggc ttc act gct gtg gcc 1227 Arg Asn Pro Ser Phe Val Leu Ser Ser Leu Gly Phe Thr Ala Val Ala 270 275 280 ttt gtc acg ggc tcc ctg gct ctg tgg gct ccg gca ttc ctg ctg cgt 1275 Phe Val Thr Gly Ser Leu Ala Leu Trp Ala Pro Ala Phe Leu Leu Arg 285 290 295 300 tcc cgc gtg gtc ctt ggg gag acc cca ccc tgc ctt ccc gga gac tcc 1323 Ser Arg Val Val Leu Gly Glu Thr Pro Pro Cys Leu Pro Gly Asp Ser 305 310 315 tgc tct tcc tct gac agt ctc atc ttt gga ctc atc acc tgc ctg acc 1371 Cys Ser Ser Ser Asp Ser Leu Ile Phe Gly Leu Ile Thr Cys Leu Thr 320 325 330 gga gtc ctg ggt gtg ggc ctg ggt gtg gag atc agc cgc cgg ctc cgc 1419 Gly Val Leu Gly Val Gly Leu Gly Val Glu Ile Ser Arg Arg Leu Arg 335 340 345 cac tcc aac ccc cgg gct gat ccc ctg gtc tgt gcc act ggc ctc ctg 1467 His Ser Asn Pro Arg Ala Asp Pro Leu Val Cys Ala Thr Gly Leu Leu 350 355 360 ggc tct gca ccc ttc ctc ttc ctg tcc ctt gcc tgc gcc cgt ggt agc 1515 Gly Ser Ala Pro Phe Leu Phe Leu Ser Leu Ala Cys Ala Arg Gly Ser 365 370 375 380 atc gtg gcc act tat att ttc atc ttc att gga gag acc ctc ctg tcc 1563 Ile Val Ala Thr Tyr Ile Phe Ile Phe Ile Gly Glu Thr Leu Leu Ser 385 390 395 atg aac tgg gcc atc gtg gcc gac att ctg ctg tac gtg gtg atc cct 1611 Met Asn Trp Ala Ile Val Ala Asp Ile Leu Leu Tyr Val Val Ile Pro 400 405 410 acc cga cgc tcc acc gcc gag gcc ttc cag atc gtg ctg tcc cac ctg 1659 Thr Arg Arg Ser Thr Ala Glu Ala Phe Gln Ile Val Leu Ser His Leu 415 420 425 ctg ggt gat gct ggg agc ccc tac ctc att ggc ctg atc tct gac cgc 1707 Leu Gly Asp Ala Gly Ser Pro Tyr Leu Ile Gly Leu Ile Ser Asp Arg 430 435 440 ctg cgc cgg aac tgg ccc ccc tcc ttc ttg tcc gag ttc cgg gct ctg 1755 Leu Arg Arg Asn Trp Pro Pro Ser Phe Leu Ser Glu Phe Arg Ala Leu 445 450 455 460 cag ttc tcg ctc atg ctc tgc gcg ttt gtt ggg gca ctg ggc ggc gca 1803 Gln Phe Ser Leu Met Leu Cys Ala Phe Val Gly Ala Leu Gly Gly Ala 465 470 475 gcc ttc ctg ggc acc gcc atc ttc att gag gcc gac cgc cgg cgg gca 1851 Ala Phe Leu Gly Thr Ala Ile Phe Ile Glu Ala Asp Arg Arg Arg Ala 480 485 490 cag ctg cac gtg cag ggc ctg ctg cac gaa gca ggg tcc aca gac gac 1899 Gln Leu His Val Gln Gly Leu Leu His Glu Ala Gly Ser Thr Asp Asp 495 500 505 cgg att gtg gtg ccc cag cgg ggc cgc tcc acc cgc gtg ccc gtg gcc 1947 Arg Ile Val Val Pro Gln Arg Gly Arg Ser Thr Arg Val Pro Val Ala 510 515 520 agt gtg ctc atc tga gaggctgccg ctcacctacc tgcacatctg ccacagctgg 2002 Ser Val Leu Ile * 525 ccctgggccc accccacgaa gggcctgggc ctaacccctt ggcctggccc agcttccaga 2062 gggaccctgg gccgtgtgcc agctcccaga cactacatgg gtagctcagg ggaggaggtg 2122 ggggtccagg agggggatcc ctctccacag gggcagcccc aagggctcgg tgctatttgt 2182 aacggaataa aatttgtagc cagaaaaaaa aaaaaaaagg gcggccgc 2230 <210> SEQ ID NO 5 <211> LENGTH: 528 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 5 Met Ala Gly Ser Asp Thr Ala Pro Phe Leu Ser Gln Ala Asp Asp Pro 1 5 10 15 Asp Asp Gly Pro Val Pro Gly Thr Pro Gly Leu Pro Gly Ser Thr Gly 20 25 30 Asn Pro Lys Ser Glu Glu Pro Glu Val Pro Asp Gln Glu Gly Leu Gln 35 40 45 Arg Ile Thr Gly Leu Ser Pro Gly Arg Ser Ala Leu Ile Val Ala Val 50 55 60 Leu Cys Tyr Ile Asn Leu Leu Asn Tyr Met Asp Arg Phe Thr Val Ala 65 70 75 80 Gly Val Leu Pro Asp Ile Glu Gln Phe Phe Asn Ile Gly Asp Ser Ser 85 90 95 Ser Gly Leu Ile Gln Thr Val Phe Ile Ser Ser Tyr Met Val Leu Ala 100 105 110 Pro Val Phe Gly Tyr Leu Gly Asp Arg Tyr Asn Arg Lys Tyr Leu Met 115 120 125 Cys Gly Gly Ile Ala Phe Trp Ser Leu Val Thr Leu Gly Ser Ser Phe 130 135 140 Ile Pro Gly Glu His Phe Trp Leu Leu Leu Leu Thr Arg Gly Leu Val 145 150 155 160 Gly Val Gly Glu Ala Ser Tyr Ser Thr Ile Ala Pro Thr Leu Ile Ala 165 170 175 Asp Leu Phe Val Ala Asp Gln Arg Ser Arg Met Leu Ser Ile Phe Tyr 180 185 190 Phe Ala Ile Pro Val Gly Ser Gly Leu Gly Tyr Ile Ala Gly Ser Lys 195 200 205 Val Lys Asp Met Ala Gly Asp Trp His Trp Ala Leu Arg Val Thr Pro 210 215 220 Gly Leu Gly Val Val Ala Val Leu Leu Leu Phe Leu Val Val Arg Glu 225 230 235 240 Pro Pro Arg Gly Ala Val Glu Arg His Ser Asp Leu Pro Pro Leu Asn 245 250 255 Pro Thr Ser Trp Trp Ala Asp Leu Arg Ala Leu Ala Arg Asn Pro Ser 260 265 270 Phe Val Leu Ser Ser Leu Gly Phe Thr Ala Val Ala Phe Val Thr Gly 275 280 285 Ser Leu Ala Leu Trp Ala Pro Ala Phe Leu Leu Arg Ser Arg Val Val 290 295 300 Leu Gly Glu Thr Pro Pro Cys Leu Pro Gly Asp Ser Cys Ser Ser Ser 305 310 315 320 Asp Ser Leu Ile Phe Gly Leu Ile Thr Cys Leu Thr Gly Val Leu Gly 325 330 335 Val Gly Leu Gly Val Glu Ile Ser Arg Arg Leu Arg His Ser Asn Pro 340 345 350 Arg Ala Asp Pro Leu Val Cys Ala Thr Gly Leu Leu Gly Ser Ala Pro 355 360 365 Phe Leu Phe Leu Ser Leu Ala Cys Ala Arg Gly Ser Ile Val Ala Thr 370 375 380 Tyr Ile Phe Ile Phe Ile Gly Glu Thr Leu Leu Ser Met Asn Trp Ala 385 390 395 400 Ile Val Ala Asp Ile Leu Leu Tyr Val Val Ile Pro Thr Arg Arg Ser 405 410 415 Thr Ala Glu Ala Phe Gln Ile Val Leu Ser His Leu Leu Gly Asp Ala 420 425 430 Gly Ser Pro Tyr Leu Ile Gly Leu Ile Ser Asp Arg Leu Arg Arg Asn 435 440 445 Trp Pro Pro Ser Phe Leu Ser Glu Phe Arg Ala Leu Gln Phe Ser Leu 450 455 460 Met Leu Cys Ala Phe Val Gly Ala Leu Gly Gly Ala Ala Phe Leu Gly 465 470 475 480 Thr Ala Ile Phe Ile Glu Ala Asp Arg Arg Arg Ala Gln Leu His Val 485 490 495 Gln Gly Leu Leu His Glu Ala Gly Ser Thr Asp Asp Arg Ile Val Val 500 505 510 Pro Gln Arg Gly Arg Ser Thr Arg Val Pro Val Ala Ser Val Leu Ile 515 520 525 <210> SEQ ID NO 6 <211> LENGTH: 1587 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(1587) <400> SEQUENCE: 6 atg gcc ggg tcc gac acc gcg ccc ttc ctc agc cag gcg gat gac ccg 48 Met Ala Gly Ser Asp Thr Ala Pro Phe Leu Ser Gln Ala Asp Asp Pro 1 5 10 15 gac gac ggg cca gtg cct ggc acc ccg ggg ttg cca ggg tcc acg ggg 96 Asp Asp Gly Pro Val Pro Gly Thr Pro Gly Leu Pro Gly Ser Thr Gly 20 25 30 aac ccg aag tcc gag gag ccc gag gtc ccg gac cag gag ggg ctg cag 144 Asn Pro Lys Ser Glu Glu Pro Glu Val Pro Asp Gln Glu Gly Leu Gln 35 40 45 cgc atc acc ggc ctg tct ccc ggc cgt tcg gct ctc ata gtg gcg gtg 192 Arg Ile Thr Gly Leu Ser Pro Gly Arg Ser Ala Leu Ile Val Ala Val 50 55 60 ctg tgc tac atc aat ctc ctg aac tac atg gac cgc ttc acc gtg gct 240 Leu Cys Tyr Ile Asn Leu Leu Asn Tyr Met Asp Arg Phe Thr Val Ala 65 70 75 80 ggc gtc ctt ccc gac atc gag cag ttc ttc aac atc ggg gac agt agc 288 Gly Val Leu Pro Asp Ile Glu Gln Phe Phe Asn Ile Gly Asp Ser Ser 85 90 95 tct ggg ctc atc cag acc gtg ttc atc tcc agt tac atg gtg ttg gca 336 Ser Gly Leu Ile Gln Thr Val Phe Ile Ser Ser Tyr Met Val Leu Ala 100 105 110 cct gtg ttt ggc tac ctg ggt gac agg tac aat cgg aag tat ctc atg 384 Pro Val Phe Gly Tyr Leu Gly Asp Arg Tyr Asn Arg Lys Tyr Leu Met 115 120 125 tgc ggg ggc att gcc ttc tgg tcc ctg gtg aca ctg ggg tca tcc ttc 432 Cys Gly Gly Ile Ala Phe Trp Ser Leu Val Thr Leu Gly Ser Ser Phe 130 135 140 atc ccc gga gag cat ttc tgg ctg ctc ctc ctg acc cgg ggc ctg gtg 480 Ile Pro Gly Glu His Phe Trp Leu Leu Leu Leu Thr Arg Gly Leu Val 145 150 155 160 ggg gtc ggg gag gcc agt tat tcc acc atc gcg ccc act ctc att gcc 528 Gly Val Gly Glu Ala Ser Tyr Ser Thr Ile Ala Pro Thr Leu Ile Ala 165 170 175 gac ctc ttt gtg gcc gac cag cgg agc cgg atg ctc agc atc ttc tac 576 Asp Leu Phe Val Ala Asp Gln Arg Ser Arg Met Leu Ser Ile Phe Tyr 180 185 190 ttt gcc att ccg gtg ggc agt ggt ctg ggc tac att gca ggc tcc aaa 624 Phe Ala Ile Pro Val Gly Ser Gly Leu Gly Tyr Ile Ala Gly Ser Lys 195 200 205 gtg aag gat atg gct gga gac tgg cac tgg gct ctg agg gtg aca ccg 672 Val Lys Asp Met Ala Gly Asp Trp His Trp Ala Leu Arg Val Thr Pro 210 215 220 ggt cta gga gtg gtg gcc gtt ctg ctg ctg ttc ctg gta gtg cgg gag 720 Gly Leu Gly Val Val Ala Val Leu Leu Leu Phe Leu Val Val Arg Glu 225 230 235 240 ccg cca agg gga gcc gtg gag cgc cac tca gat ttg cca ccc ctg aac 768 Pro Pro Arg Gly Ala Val Glu Arg His Ser Asp Leu Pro Pro Leu Asn 245 250 255 ccc acc tcg tgg tgg gca gat ctg agg gct ctg gca aga aat cct agt 816 Pro Thr Ser Trp Trp Ala Asp Leu Arg Ala Leu Ala Arg Asn Pro Ser 260 265 270 ttc gtc ctg tct tcc ctg ggc ttc act gct gtg gcc ttt gtc acg ggc 864 Phe Val Leu Ser Ser Leu Gly Phe Thr Ala Val Ala Phe Val Thr Gly 275 280 285 tcc ctg gct ctg tgg gct ccg gca ttc ctg ctg cgt tcc cgc gtg gtc 912 Ser Leu Ala Leu Trp Ala Pro Ala Phe Leu Leu Arg Ser Arg Val Val 290 295 300 ctt ggg gag acc cca ccc tgc ctt ccc gga gac tcc tgc tct tcc tct 960 Leu Gly Glu Thr Pro Pro Cys Leu Pro Gly Asp Ser Cys Ser Ser Ser 305 310 315 320 gac agt ctc atc ttt gga ctc atc acc tgc ctg acc gga gtc ctg ggt 1008 Asp Ser Leu Ile Phe Gly Leu Ile Thr Cys Leu Thr Gly Val Leu Gly 325 330 335 gtg ggc ctg ggt gtg gag atc agc cgc cgg ctc cgc cac tcc aac ccc 1056 Val Gly Leu Gly Val Glu Ile Ser Arg Arg Leu Arg His Ser Asn Pro 340 345 350 cgg gct gat ccc ctg gtc tgt gcc act ggc ctc ctg ggc tct gca ccc 1104 Arg Ala Asp Pro Leu Val Cys Ala Thr Gly Leu Leu Gly Ser Ala Pro 355 360 365 ttc ctc ttc ctg tcc ctt gcc tgc gcc cgt ggt agc atc gtg gcc act 1152 Phe Leu Phe Leu Ser Leu Ala Cys Ala Arg Gly Ser Ile Val Ala Thr 370 375 380 tat att ttc atc ttc att gga gag acc ctc ctg tcc atg aac tgg gcc 1200 Tyr Ile Phe Ile Phe Ile Gly Glu Thr Leu Leu Ser Met Asn Trp Ala 385 390 395 400 atc gtg gcc gac att ctg ctg tac gtg gtg atc cct acc cga cgc tcc 1248 Ile Val Ala Asp Ile Leu Leu Tyr Val Val Ile Pro Thr Arg Arg Ser 405 410 415 acc gcc gag gcc ttc cag atc gtg ctg tcc cac ctg ctg ggt gat gct 1296 Thr Ala Glu Ala Phe Gln Ile Val Leu Ser His Leu Leu Gly Asp Ala 420 425 430 ggg agc ccc tac ctc att ggc ctg atc tct gac cgc ctg cgc cgg aac 1344 Gly Ser Pro Tyr Leu Ile Gly Leu Ile Ser Asp Arg Leu Arg Arg Asn 435 440 445 tgg ccc ccc tcc ttc ttg tcc gag ttc cgg gct ctg cag ttc tcg ctc 1392 Trp Pro Pro Ser Phe Leu Ser Glu Phe Arg Ala Leu Gln Phe Ser Leu 450 455 460 atg ctc tgc gcg ttt gtt ggg gca ctg ggc ggc gca gcc ttc ctg ggc 1440 Met Leu Cys Ala Phe Val Gly Ala Leu Gly Gly Ala Ala Phe Leu Gly 465 470 475 480 acc gcc atc ttc att gag gcc gac cgc cgg cgg gca cag ctg cac gtg 1488 Thr Ala Ile Phe Ile Glu Ala Asp Arg Arg Arg Ala Gln Leu His Val 485 490 495 cag ggc ctg ctg cac gaa gca ggg tcc aca gac gac cgg att gtg gtg 1536 Gln Gly Leu Leu His Glu Ala Gly Ser Thr Asp Asp Arg Ile Val Val 500 505 510 ccc cag cgg ggc cgc tcc acc cgc gtg ccc gtg gcc agt gtg ctc atc 1584 Pro Gln Arg Gly Arg Ser Thr Arg Val Pro Val Ala Ser Val Leu Ile 515 520 525 tga 1587 * <210> SEQ ID NO 7 <211> LENGTH: 4632 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (225)...(3581) <221> NAME/KEY: misc_feature <222> LOCATION: (4611) <223> OTHER INFORMATION: n = a,c,t, or g <400> SEQUENCE: 7 cacgcgtccg cccacgcgtc cgcccacgcg tccgagcccc ctttcaagcc ttagcttccg 60 gctccaagcc gaccccctcc ccctccctgt ccccttcccc ttctcccatc cctctctcgg 120 ccacagcgtc ttgttagtcc tctccctcta ctccgcaata ttttctttct ttctccctcc 180 tctcctccat ttgttgtttg atgtttccca ctctttgagg aagg atg gtt gat ttg 236 Met Val Asp Leu 1 gag agc gaa gtg ccc cct ctg cct ccc agg tac agg ttt cga gat ttg 284 Glu Ser Glu Val Pro Pro Leu Pro Pro Arg Tyr Arg Phe Arg Asp Leu 5 10 15 20 ctg cta ggg gac caa gga tgg caa aac gat gac aga gta caa gtt gaa 332 Leu Leu Gly Asp Gln Gly Trp Gln Asn Asp Asp Arg Val Gln Val Glu 25 30 35 ttc tat atg aat gaa aat aca ttt aaa gaa aga cta aaa tta ttt ttc 380 Phe Tyr Met Asn Glu Asn Thr Phe Lys Glu Arg Leu Lys Leu Phe Phe 40 45 50 ata aaa aac cag aga tca agt cta agg ata cgc ctg ttc aat ttt tct 428 Ile Lys Asn Gln Arg Ser Ser Leu Arg Ile Arg Leu Phe Asn Phe Ser 55 60 65 ctc aaa tta cta agc tgc tta tta tac ata atc cga gta cta cta gaa 476 Leu Lys Leu Leu Ser Cys Leu Leu Tyr Ile Ile Arg Val Leu Leu Glu 70 75 80 aac cct tca caa gga aat gaa tgg tct cat atc ttt tgg gtg aac aga 524 Asn Pro Ser Gln Gly Asn Glu Trp Ser His Ile Phe Trp Val Asn Arg 85 90 95 100 agt cta cct ttg tgg ggc tta cag gtt tca gtg gca ttg ata agt ctg 572 Ser Leu Pro Leu Trp Gly Leu Gln Val Ser Val Ala Leu Ile Ser Leu 105 110 115 ttt gaa aca ata tta ctt ggt tat ctt agt tat aag gga aac atc tgg 620 Phe Glu Thr Ile Leu Leu Gly Tyr Leu Ser Tyr Lys Gly Asn Ile Trp 120 125 130 gaa cag att tta cga ata ccc ttc atc ttg gaa ata att aat gca gtt 668 Glu Gln Ile Leu Arg Ile Pro Phe Ile Leu Glu Ile Ile Asn Ala Val 135 140 145 ccc ttc att atc tca ata ttc tgg cct tcc tta agg aat cta ttt gtc 716 Pro Phe Ile Ile Ser Ile Phe Trp Pro Ser Leu Arg Asn Leu Phe Val 150 155 160 cca gtc ttt ctg aac tgt tgg ctt gcc aaa cat gcc ttg gaa aat atg 764 Pro Val Phe Leu Asn Cys Trp Leu Ala Lys His Ala Leu Glu Asn Met 165 170 175 180 att aat gat cta cac aga gcc att cag cgt aca cag tct gca atg ttt 812 Ile Asn Asp Leu His Arg Ala Ile Gln Arg Thr Gln Ser Ala Met Phe 185 190 195 aat caa gtt ttg att tta ata tct aca tta cta tgc ctt atc ttc acc 860 Asn Gln Val Leu Ile Leu Ile Ser Thr Leu Leu Cys Leu Ile Phe Thr 200 205 210 tgc att tgt ggg atc caa cat ctg gaa cga ata gga aag agg ctg aat 908 Cys Ile Cys Gly Ile Gln His Leu Glu Arg Ile Gly Lys Arg Leu Asn 215 220 225 ctc ttt gac tcc ctt tat ttc tgc att gtg acg ttt tct act gtg ggc 956 Leu Phe Asp Ser Leu Tyr Phe Cys Ile Val Thr Phe Ser Thr Val Gly 230 235 240 ttc ggg gat gtc act cct gaa aca tgg tcc tcc aag ctt ttt gta gtt 1004 Phe Gly Asp Val Thr Pro Glu Thr Trp Ser Ser Lys Leu Phe Val Val 245 250 255 260 gct atg att tgt gtt gct ctt gtg gtt cta ccc ata cag ttt gaa cag 1052 Ala Met Ile Cys Val Ala Leu Val Val Leu Pro Ile Gln Phe Glu Gln 265 270 275 ctg gct tat ttg tgg atg gag aga caa aag tca gga gga aac tat agt 1100 Leu Ala Tyr Leu Trp Met Glu Arg Gln Lys Ser Gly Gly Asn Tyr Ser 280 285 290 cga cat aga gct caa act gaa aag cat gtc gtc ctg tgt gtc agc tca 1148 Arg His Arg Ala Gln Thr Glu Lys His Val Val Leu Cys Val Ser Ser 295 300 305 ctg aag att gat tta ctt atg gat ttt tta aat gaa ttc tat gct cat 1196 Leu Lys Ile Asp Leu Leu Met Asp Phe Leu Asn Glu Phe Tyr Ala His 310 315 320 cct agg ctc cag gat tat tat gtg gtg att ttg tgt cct act gaa atg 1244 Pro Arg Leu Gln Asp Tyr Tyr Val Val Ile Leu Cys Pro Thr Glu Met 325 330 335 340 gat gta cag gtt cga agg gta ctg cag att cca atg tgg tcc caa cga 1292 Asp Val Gln Val Arg Arg Val Leu Gln Ile Pro Met Trp Ser Gln Arg 345 350 355 gtt atc tac ctt caa ggt tca gcc ctt aaa gat caa gac cta ttg aga 1340 Val Ile Tyr Leu Gln Gly Ser Ala Leu Lys Asp Gln Asp Leu Leu Arg 360 365 370 gca aag atg gat gac gct gag gcc tgt ttt att ctc agt agc cgt tgt 1388 Ala Lys Met Asp Asp Ala Glu Ala Cys Phe Ile Leu Ser Ser Arg Cys 375 380 385 gaa gtg gat agg aca tca tct gat cac caa aca att ttg aga gca tgg 1436 Glu Val Asp Arg Thr Ser Ser Asp His Gln Thr Ile Leu Arg Ala Trp 390 395 400 gct gtg aaa gat ttt gct cca aat tgt cct ttg tat gtc cag ata tta 1484 Ala Val Lys Asp Phe Ala Pro Asn Cys Pro Leu Tyr Val Gln Ile Leu 405 410 415 420 aag cct gaa aat aaa ttt cac atc aaa ttt gct gat cat gtt gtt tgt 1532 Lys Pro Glu Asn Lys Phe His Ile Lys Phe Ala Asp His Val Val Cys 425 430 435 gaa gaa gag ttt aaa tac gcc atg tta gct tta aac tgt ata tgc cca 1580 Glu Glu Glu Phe Lys Tyr Ala Met Leu Ala Leu Asn Cys Ile Cys Pro 440 445 450 gca aca tct aca ctt att aca cta ctg gtt cat acc tct aga ggg caa 1628 Ala Thr Ser Thr Leu Ile Thr Leu Leu Val His Thr Ser Arg Gly Gln 455 460 465 gaa ggc cag caa tcg cca gaa caa tgg cag aag atg tac ggt aga tgc 1676 Glu Gly Gln Gln Ser Pro Glu Gln Trp Gln Lys Met Tyr Gly Arg Cys 470 475 480 tcc ggg aat gaa gtc tac cac att gtt ttg gaa gaa agt aca ttt ttt 1724 Ser Gly Asn Glu Val Tyr His Ile Val Leu Glu Glu Ser Thr Phe Phe 485 490 495 500 gct gaa tat gaa gga aag agt ttt aca tat gcc tct ttc cat gca cac 1772 Ala Glu Tyr Glu Gly Lys Ser Phe Thr Tyr Ala Ser Phe His Ala His 505 510 515 aaa aag ttt ggc gtc tgc ttg att ggt gtt agg agg gag gat aat aaa 1820 Lys Lys Phe Gly Val Cys Leu Ile Gly Val Arg Arg Glu Asp Asn Lys 520 525 530 aac att ttg ctg aat cca ggt cct cga tac att atg aat tct acg gac 1868 Asn Ile Leu Leu Asn Pro Gly Pro Arg Tyr Ile Met Asn Ser Thr Asp 535 540 545 ata tgc ttt tat att aat att acc aaa gaa gag aat tca gca ttt aaa 1916 Ile Cys Phe Tyr Ile Asn Ile Thr Lys Glu Glu Asn Ser Ala Phe Lys 550 555 560 aac caa gac cag cag aga aaa agc aat gtg tcc agg tcg ttt tat cat 1964 Asn Gln Asp Gln Gln Arg Lys Ser Asn Val Ser Arg Ser Phe Tyr His 565 570 575 580 gga cct tcc aga tta cct gta cat agc ata att gcc agc atg ggt act 2012 Gly Pro Ser Arg Leu Pro Val His Ser Ile Ile Ala Ser Met Gly Thr 585 590 595 gtg gct ata gac ctg caa gat aca agc tgt aga tca gca agt ggc cct 2060 Val Ala Ile Asp Leu Gln Asp Thr Ser Cys Arg Ser Ala Ser Gly Pro 600 605 610 acc ctg tct ctt cct aca gag gga agc aaa gaa ata aga aga cct agc 2108 Thr Leu Ser Leu Pro Thr Glu Gly Ser Lys Glu Ile Arg Arg Pro Ser 615 620 625 att gct cct gtt tta gag gtt gca gat aca tca tcg att caa aca tgt 2156 Ile Ala Pro Val Leu Glu Val Ala Asp Thr Ser Ser Ile Gln Thr Cys 630 635 640 gat ctt cta agt gac caa tca gaa gat gaa act aca cca gat gaa gaa 2204 Asp Leu Leu Ser Asp Gln Ser Glu Asp Glu Thr Thr Pro Asp Glu Glu 645 650 655 660 atg tct tca aac tta gag tat gct aaa ggt tac cca cct tat tct cca 2252 Met Ser Ser Asn Leu Glu Tyr Ala Lys Gly Tyr Pro Pro Tyr Ser Pro 665 670 675 tat ata gga agt tca ccc act ttt tgt cat ctc ctt cat gaa aaa gta 2300 Tyr Ile Gly Ser Ser Pro Thr Phe Cys His Leu Leu His Glu Lys Val 680 685 690 cca ttt tgc tgc tta aga tta gac aag agt tgc caa cat aac tac tat 2348 Pro Phe Cys Cys Leu Arg Leu Asp Lys Ser Cys Gln His Asn Tyr Tyr 695 700 705 gag gat gca aaa gcc tat gga ttc aaa aat aaa cta att ata gtt gca 2396 Glu Asp Ala Lys Ala Tyr Gly Phe Lys Asn Lys Leu Ile Ile Val Ala 710 715 720 gct gaa aca gct gga aat gga tta tat aac ttt att gtt cct ctc agg 2444 Ala Glu Thr Ala Gly Asn Gly Leu Tyr Asn Phe Ile Val Pro Leu Arg 725 730 735 740 gca tat tat aga cca aag aaa gaa ctt aat ccc ata gta ctg cta ttg 2492 Ala Tyr Tyr Arg Pro Lys Lys Glu Leu Asn Pro Ile Val Leu Leu Leu 745 750 755 gat aac ccc cta gat gac tta ctc agg tgt gga gtg act ttt gct gct 2540 Asp Asn Pro Leu Asp Asp Leu Leu Arg Cys Gly Val Thr Phe Ala Ala 760 765 770 aat atg gtg gtt gtg gat aaa gag agc acc atg agt gcc gag gaa gac 2588 Asn Met Val Val Val Asp Lys Glu Ser Thr Met Ser Ala Glu Glu Asp 775 780 785 tac atg gca gat gcc aaa acc att gtg aac gtg cag aca ctc ttc agg 2636 Tyr Met Ala Asp Ala Lys Thr Ile Val Asn Val Gln Thr Leu Phe Arg 790 795 800 ttg ttt tcc agt ctc agt att atc aca gag cta act cac ccc gcc aac 2684 Leu Phe Ser Ser Leu Ser Ile Ile Thr Glu Leu Thr His Pro Ala Asn 805 810 815 820 atg aga ttc atg caa ttc aga gcc aaa gac tgt tac tct ctt gct ctt 2732 Met Arg Phe Met Gln Phe Arg Ala Lys Asp Cys Tyr Ser Leu Ala Leu 825 830 835 tca aaa ctg gaa aag aaa gaa cgg gag aga ggc tct aac ttg gcc ttt 2780 Ser Lys Leu Glu Lys Lys Glu Arg Glu Arg Gly Ser Asn Leu Ala Phe 840 845 850 atg ttt cga ctg cct ttt gct gct ggg agg gtg ttt agc atc agt atg 2828 Met Phe Arg Leu Pro Phe Ala Ala Gly Arg Val Phe Ser Ile Ser Met 855 860 865 ttg gac act ctg ctg tat cag tca ttt gtg aag gat tat atg att tct 2876 Leu Asp Thr Leu Leu Tyr Gln Ser Phe Val Lys Asp Tyr Met Ile Ser 870 875 880 atc acg aga ctt ctg ttg gga ctg gac act aca cca gga tct ggg ttt 2924 Ile Thr Arg Leu Leu Leu Gly Leu Asp Thr Thr Pro Gly Ser Gly Phe 885 890 895 900 ctt tgt tct atg aaa atc act gca gat gac tta tgg atc aga act tat 2972 Leu Cys Ser Met Lys Ile Thr Ala Asp Asp Leu Trp Ile Arg Thr Tyr 905 910 915 gcc aga ctt tat cag aag ttg tgt tct tct act gga gat gtt ccc att 3020 Ala Arg Leu Tyr Gln Lys Leu Cys Ser Ser Thr Gly Asp Val Pro Ile 920 925 930 gga atc tac agg act gag tct cag aaa ctt act aca tct gag tct cga 3068 Gly Ile Tyr Arg Thr Glu Ser Gln Lys Leu Thr Thr Ser Glu Ser Arg 935 940 945 aaa ata gca tca caa tct caa ata tct atc agt gta gaa gag tgg gaa 3116 Lys Ile Ala Ser Gln Ser Gln Ile Ser Ile Ser Val Glu Glu Trp Glu 950 955 960 gac acc aaa gac tcc aaa gaa caa ggg cac cac cgc agc aac cac cgc 3164 Asp Thr Lys Asp Ser Lys Glu Gln Gly His His Arg Ser Asn His Arg 965 970 975 980 aac tca aca tcc agt gac cag tcg gac cat ccc ttg ctg cgg aga aaa 3212 Asn Ser Thr Ser Ser Asp Gln Ser Asp His Pro Leu Leu Arg Arg Lys 985 990 995 agc atg cag tgg gcc cga aga ctg agc aga aaa ggc cca aaa cac tct 3260 Ser Met Gln Trp Ala Arg Arg Leu Ser Arg Lys Gly Pro Lys His Ser 1000 1005 1010 ggt aaa aca gct gaa aaa ata acc cag cag cga ctg aac ctc tac agg 3308 Gly Lys Thr Ala Glu Lys Ile Thr Gln Gln Arg Leu Asn Leu Tyr Arg 1015 1020 1025 agg tca gaa aga caa gag ctt gct gaa ctt gtg aaa aat aga atg aaa 3356 Arg Ser Glu Arg Gln Glu Leu Ala Glu Leu Val Lys Asn Arg Met Lys 1030 1035 1040 cac ttg ggt ctt tct aca gtg gga tat gat gaa atg aat gat cat caa 3404 His Leu Gly Leu Ser Thr Val Gly Tyr Asp Glu Met Asn Asp His Gln 1045 1050 1055 1060 agt acc ctc tcc tac atc ctg att aac cca tct cca gat acc aga ata 3452 Ser Thr Leu Ser Tyr Ile Leu Ile Asn Pro Ser Pro Asp Thr Arg Ile 1065 1070 1075 gag ctg aat gat gtt gta tac tta att cga cca gat cca ctg gcc tac 3500 Glu Leu Asn Asp Val Val Tyr Leu Ile Arg Pro Asp Pro Leu Ala Tyr 1080 1085 1090 ctt cca aac agt gag ccc agt cga aga aac agc atc tgc aat gtc act 3548 Leu Pro Asn Ser Glu Pro Ser Arg Arg Asn Ser Ile Cys Asn Val Thr 1095 1100 1105 ggt caa gat tct cgg gag gaa act caa ctt tga taaaaataaa atgagaaact 3601 Gly Gln Asp Ser Arg Glu Glu Thr Gln Leu * 1110 1115 tttttcctac aaagaccttg cttgaaacca caaaagtttt gctggcacga aagaaactag 3661 atggaaatat atgtaattct ctcatattta aaaacgtaat ctcttctctt agaagtatag 3721 atcattttga aacttaatgt actacttact ggtactctcc ctattaatat ttgaaggacc 3781 tcaatggaat aaatttgaaa agctaaatta aaatacaaaa atttaaatct gacatttaat 3841 tgttttataa taatccaaac tctatgaaag caattttaaa aattattaag gttttatgaa 3901 gttgacaaaa tctaactata tttggtgcat cacaatggac acagaatgct gctgctcctc 3961 ttaaaaatta aatgtgtcat attatattct ttaaacttac tgttttacaa aattgagctc 4021 atcgtaaatg tctagtcttc tcacatagag attaaccaac aaacttgtgt ggctgacttt 4081 tgtgtaagaa tcatagtttg ctttagaata caaatcttta agtcatttta actttttttt 4141 ctgccttacg atataaaaat atttatctta gaatttgaga tgttcatagc atgttttatt 4201 acattgaaga aactaaaaca taaatgaaaa gaaacactag gttcctgcac tttttggtaa 4261 ctttatgtct agcaaatatt ttatgccaag aaaagcatac tataaagcaa atatctatta 4321 ttctcctaaa cgaatgccta gcatagagaa aatacttaat acacatttgt tgacttaaat 4381 ttaattcaag gattgaaaaa ttaactggat atcttgaaat atacagtaat gattgtcctt 4441 agactcttga actttaccat ctttcctatt catatatcta tatagtaaat ttcactagaa 4501 aaattctttt aaaattgaca gaagataatt tatacctttt atggactctg aagacacttc 4561 aaaacattaa aagtccttat gtctttggta atgaaacata cactcaatga ngatgtatta 4621 aattttgact t 4632 <210> SEQ ID NO 8 <211> LENGTH: 1118 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 8 Met Val Asp Leu Glu Ser Glu Val Pro Pro Leu Pro Pro Arg Tyr Arg 1 5 10 15 Phe Arg Asp Leu Leu Leu Gly Asp Gln Gly Trp Gln Asn Asp Asp Arg 20 25 30 Val Gln Val Glu Phe Tyr Met Asn Glu Asn Thr Phe Lys Glu Arg Leu 35 40 45 Lys Leu Phe Phe Ile Lys Asn Gln Arg Ser Ser Leu Arg Ile Arg Leu 50 55 60 Phe Asn Phe Ser Leu Lys Leu Leu Ser Cys Leu Leu Tyr Ile Ile Arg 65 70 75 80 Val Leu Leu Glu Asn Pro Ser Gln Gly Asn Glu Trp Ser His Ile Phe 85 90 95 Trp Val Asn Arg Ser Leu Pro Leu Trp Gly Leu Gln Val Ser Val Ala 100 105 110 Leu Ile Ser Leu Phe Glu Thr Ile Leu Leu Gly Tyr Leu Ser Tyr Lys 115 120 125 Gly Asn Ile Trp Glu Gln Ile Leu Arg Ile Pro Phe Ile Leu Glu Ile 130 135 140 Ile Asn Ala Val Pro Phe Ile Ile Ser Ile Phe Trp Pro Ser Leu Arg 145 150 155 160 Asn Leu Phe Val Pro Val Phe Leu Asn Cys Trp Leu Ala Lys His Ala 165 170 175 Leu Glu Asn Met Ile Asn Asp Leu His Arg Ala Ile Gln Arg Thr Gln 180 185 190 Ser Ala Met Phe Asn Gln Val Leu Ile Leu Ile Ser Thr Leu Leu Cys 195 200 205 Leu Ile Phe Thr Cys Ile Cys Gly Ile Gln His Leu Glu Arg Ile Gly 210 215 220 Lys Arg Leu Asn Leu Phe Asp Ser Leu Tyr Phe Cys Ile Val Thr Phe 225 230 235 240 Ser Thr Val Gly Phe Gly Asp Val Thr Pro Glu Thr Trp Ser Ser Lys 245 250 255 Leu Phe Val Val Ala Met Ile Cys Val Ala Leu Val Val Leu Pro Ile 260 265 270 Gln Phe Glu Gln Leu Ala Tyr Leu Trp Met Glu Arg Gln Lys Ser Gly 275 280 285 Gly Asn Tyr Ser Arg His Arg Ala Gln Thr Glu Lys His Val Val Leu 290 295 300 Cys Val Ser Ser Leu Lys Ile Asp Leu Leu Met Asp Phe Leu Asn Glu 305 310 315 320 Phe Tyr Ala His Pro Arg Leu Gln Asp Tyr Tyr Val Val Ile Leu Cys 325 330 335 Pro Thr Glu Met Asp Val Gln Val Arg Arg Val Leu Gln Ile Pro Met 340 345 350 Trp Ser Gln Arg Val Ile Tyr Leu Gln Gly Ser Ala Leu Lys Asp Gln 355 360 365 Asp Leu Leu Arg Ala Lys Met Asp Asp Ala Glu Ala Cys Phe Ile Leu 370 375 380 Ser Ser Arg Cys Glu Val Asp Arg Thr Ser Ser Asp His Gln Thr Ile 385 390 395 400 Leu Arg Ala Trp Ala Val Lys Asp Phe Ala Pro Asn Cys Pro Leu Tyr 405 410 415 Val Gln Ile Leu Lys Pro Glu Asn Lys Phe His Ile Lys Phe Ala Asp 420 425 430 His Val Val Cys Glu Glu Glu Phe Lys Tyr Ala Met Leu Ala Leu Asn 435 440 445 Cys Ile Cys Pro Ala Thr Ser Thr Leu Ile Thr Leu Leu Val His Thr 450 455 460 Ser Arg Gly Gln Glu Gly Gln Gln Ser Pro Glu Gln Trp Gln Lys Met 465 470 475 480 Tyr Gly Arg Cys Ser Gly Asn Glu Val Tyr His Ile Val Leu Glu Glu 485 490 495 Ser Thr Phe Phe Ala Glu Tyr Glu Gly Lys Ser Phe Thr Tyr Ala Ser 500 505 510 Phe His Ala His Lys Lys Phe Gly Val Cys Leu Ile Gly Val Arg Arg 515 520 525 Glu Asp Asn Lys Asn Ile Leu Leu Asn Pro Gly Pro Arg Tyr Ile Met 530 535 540 Asn Ser Thr Asp Ile Cys Phe Tyr Ile Asn Ile Thr Lys Glu Glu Asn 545 550 555 560 Ser Ala Phe Lys Asn Gln Asp Gln Gln Arg Lys Ser Asn Val Ser Arg 565 570 575 Ser Phe Tyr His Gly Pro Ser Arg Leu Pro Val His Ser Ile Ile Ala 580 585 590 Ser Met Gly Thr Val Ala Ile Asp Leu Gln Asp Thr Ser Cys Arg Ser 595 600 605 Ala Ser Gly Pro Thr Leu Ser Leu Pro Thr Glu Gly Ser Lys Glu Ile 610 615 620 Arg Arg Pro Ser Ile Ala Pro Val Leu Glu Val Ala Asp Thr Ser Ser 625 630 635 640 Ile Gln Thr Cys Asp Leu Leu Ser Asp Gln Ser Glu Asp Glu Thr Thr 645 650 655 Pro Asp Glu Glu Met Ser Ser Asn Leu Glu Tyr Ala Lys Gly Tyr Pro 660 665 670 Pro Tyr Ser Pro Tyr Ile Gly Ser Ser Pro Thr Phe Cys His Leu Leu 675 680 685 His Glu Lys Val Pro Phe Cys Cys Leu Arg Leu Asp Lys Ser Cys Gln 690 695 700 His Asn Tyr Tyr Glu Asp Ala Lys Ala Tyr Gly Phe Lys Asn Lys Leu 705 710 715 720 Ile Ile Val Ala Ala Glu Thr Ala Gly Asn Gly Leu Tyr Asn Phe Ile 725 730 735 Val Pro Leu Arg Ala Tyr Tyr Arg Pro Lys Lys Glu Leu Asn Pro Ile 740 745 750 Val Leu Leu Leu Asp Asn Pro Leu Asp Asp Leu Leu Arg Cys Gly Val 755 760 765 Thr Phe Ala Ala Asn Met Val Val Val Asp Lys Glu Ser Thr Met Ser 770 775 780 Ala Glu Glu Asp Tyr Met Ala Asp Ala Lys Thr Ile Val Asn Val Gln 785 790 795 800 Thr Leu Phe Arg Leu Phe Ser Ser Leu Ser Ile Ile Thr Glu Leu Thr 805 810 815 His Pro Ala Asn Met Arg Phe Met Gln Phe Arg Ala Lys Asp Cys Tyr 820 825 830 Ser Leu Ala Leu Ser Lys Leu Glu Lys Lys Glu Arg Glu Arg Gly Ser 835 840 845 Asn Leu Ala Phe Met Phe Arg Leu Pro Phe Ala Ala Gly Arg Val Phe 850 855 860 Ser Ile Ser Met Leu Asp Thr Leu Leu Tyr Gln Ser Phe Val Lys Asp 865 870 875 880 Tyr Met Ile Ser Ile Thr Arg Leu Leu Leu Gly Leu Asp Thr Thr Pro 885 890 895 Gly Ser Gly Phe Leu Cys Ser Met Lys Ile Thr Ala Asp Asp Leu Trp 900 905 910 Ile Arg Thr Tyr Ala Arg Leu Tyr Gln Lys Leu Cys Ser Ser Thr Gly 915 920 925 Asp Val Pro Ile Gly Ile Tyr Arg Thr Glu Ser Gln Lys Leu Thr Thr 930 935 940 Ser Glu Ser Arg Lys Ile Ala Ser Gln Ser Gln Ile Ser Ile Ser Val 945 950 955 960 Glu Glu Trp Glu Asp Thr Lys Asp Ser Lys Glu Gln Gly His His Arg 965 970 975 Ser Asn His Arg Asn Ser Thr Ser Ser Asp Gln Ser Asp His Pro Leu 980 985 990 Leu Arg Arg Lys Ser Met Gln Trp Ala Arg Arg Leu Ser Arg Lys Gly 995 1000 1005 Pro Lys His Ser Gly Lys Thr Ala Glu Lys Ile Thr Gln Gln Arg Leu 1010 1015 1020 Asn Leu Tyr Arg Arg Ser Glu Arg Gln Glu Leu Ala Glu Leu Val Lys 1025 1030 1035 1040 Asn Arg Met Lys His Leu Gly Leu Ser Thr Val Gly Tyr Asp Glu Met 1045 1050 1055 Asn Asp His Gln Ser Thr Leu Ser Tyr Ile Leu Ile Asn Pro Ser Pro 1060 1065 1070 Asp Thr Arg Ile Glu Leu Asn Asp Val Val Tyr Leu Ile Arg Pro Asp 1075 1080 1085 Pro Leu Ala Tyr Leu Pro Asn Ser Glu Pro Ser Arg Arg Asn Ser Ile 1090 1095 1100 Cys Asn Val Thr Gly Gln Asp Ser Arg Glu Glu Thr Gln Leu 1105 1110 1115 <210> SEQ ID NO 9 <211> LENGTH: 3357 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(3357) <400> SEQUENCE: 9 atg gtt gat ttg gag agc gaa gtg ccc cct ctg cct ccc agg tac agg 48 Met Val Asp Leu Glu Ser Glu Val Pro Pro Leu Pro Pro Arg Tyr Arg 1 5 10 15 ttt cga gat ttg ctg cta ggg gac caa gga tgg caa aac gat gac aga 96 Phe Arg Asp Leu Leu Leu Gly Asp Gln Gly Trp Gln Asn Asp Asp Arg 20 25 30 gta caa gtt gaa ttc tat atg aat gaa aat aca ttt aaa gaa aga cta 144 Val Gln Val Glu Phe Tyr Met Asn Glu Asn Thr Phe Lys Glu Arg Leu 35 40 45 aaa tta ttt ttc ata aaa aac cag aga tca agt cta agg ata cgc ctg 192 Lys Leu Phe Phe Ile Lys Asn Gln Arg Ser Ser Leu Arg Ile Arg Leu 50 55 60 ttc aat ttt tct ctc aaa tta cta agc tgc tta tta tac ata atc cga 240 Phe Asn Phe Ser Leu Lys Leu Leu Ser Cys Leu Leu Tyr Ile Ile Arg 65 70 75 80 gta cta cta gaa aac cct tca caa gga aat gaa tgg tct cat atc ttt 288 Val Leu Leu Glu Asn Pro Ser Gln Gly Asn Glu Trp Ser His Ile Phe 85 90 95 tgg gtg aac aga agt cta cct ttg tgg ggc tta cag gtt tca gtg gca 336 Trp Val Asn Arg Ser Leu Pro Leu Trp Gly Leu Gln Val Ser Val Ala 100 105 110 ttg ata agt ctg ttt gaa aca ata tta ctt ggt tat ctt agt tat aag 384 Leu Ile Ser Leu Phe Glu Thr Ile Leu Leu Gly Tyr Leu Ser Tyr Lys 115 120 125 gga aac atc tgg gaa cag att tta cga ata ccc ttc atc ttg gaa ata 432 Gly Asn Ile Trp Glu Gln Ile Leu Arg Ile Pro Phe Ile Leu Glu Ile 130 135 140 att aat gca gtt ccc ttc att atc tca ata ttc tgg cct tcc tta agg 480 Ile Asn Ala Val Pro Phe Ile Ile Ser Ile Phe Trp Pro Ser Leu Arg 145 150 155 160 aat cta ttt gtc cca gtc ttt ctg aac tgt tgg ctt gcc aaa cat gcc 528 Asn Leu Phe Val Pro Val Phe Leu Asn Cys Trp Leu Ala Lys His Ala 165 170 175 ttg gaa aat atg att aat gat cta cac aga gcc att cag cgt aca cag 576 Leu Glu Asn Met Ile Asn Asp Leu His Arg Ala Ile Gln Arg Thr Gln 180 185 190 tct gca atg ttt aat caa gtt ttg att tta ata tct aca tta cta tgc 624 Ser Ala Met Phe Asn Gln Val Leu Ile Leu Ile Ser Thr Leu Leu Cys 195 200 205 ctt atc ttc acc tgc att tgt ggg atc caa cat ctg gaa cga ata gga 672 Leu Ile Phe Thr Cys Ile Cys Gly Ile Gln His Leu Glu Arg Ile Gly 210 215 220 aag agg ctg aat ctc ttt gac tcc ctt tat ttc tgc att gtg acg ttt 720 Lys Arg Leu Asn Leu Phe Asp Ser Leu Tyr Phe Cys Ile Val Thr Phe 225 230 235 240 tct act gtg ggc ttc ggg gat gtc act cct gaa aca tgg tcc tcc aag 768 Ser Thr Val Gly Phe Gly Asp Val Thr Pro Glu Thr Trp Ser Ser Lys 245 250 255 ctt ttt gta gtt gct atg att tgt gtt gct ctt gtg gtt cta ccc ata 816 Leu Phe Val Val Ala Met Ile Cys Val Ala Leu Val Val Leu Pro Ile 260 265 270 cag ttt gaa cag ctg gct tat ttg tgg atg gag aga caa aag tca gga 864 Gln Phe Glu Gln Leu Ala Tyr Leu Trp Met Glu Arg Gln Lys Ser Gly 275 280 285 gga aac tat agt cga cat aga gct caa act gaa aag cat gtc gtc ctg 912 Gly Asn Tyr Ser Arg His Arg Ala Gln Thr Glu Lys His Val Val Leu 290 295 300 tgt gtc agc tca ctg aag att gat tta ctt atg gat ttt tta aat gaa 960 Cys Val Ser Ser Leu Lys Ile Asp Leu Leu Met Asp Phe Leu Asn Glu 305 310 315 320 ttc tat gct cat cct agg ctc cag gat tat tat gtg gtg att ttg tgt 1008 Phe Tyr Ala His Pro Arg Leu Gln Asp Tyr Tyr Val Val Ile Leu Cys 325 330 335 cct act gaa atg gat gta cag gtt cga agg gta ctg cag att cca atg 1056 Pro Thr Glu Met Asp Val Gln Val Arg Arg Val Leu Gln Ile Pro Met 340 345 350 tgg tcc caa cga gtt atc tac ctt caa ggt tca gcc ctt aaa gat caa 1104 Trp Ser Gln Arg Val Ile Tyr Leu Gln Gly Ser Ala Leu Lys Asp Gln 355 360 365 gac cta ttg aga gca aag atg gat gac gct gag gcc tgt ttt att ctc 1152 Asp Leu Leu Arg Ala Lys Met Asp Asp Ala Glu Ala Cys Phe Ile Leu 370 375 380 agt agc cgt tgt gaa gtg gat agg aca tca tct gat cac caa aca att 1200 Ser Ser Arg Cys Glu Val Asp Arg Thr Ser Ser Asp His Gln Thr Ile 385 390 395 400 ttg aga gca tgg gct gtg aaa gat ttt gct cca aat tgt cct ttg tat 1248 Leu Arg Ala Trp Ala Val Lys Asp Phe Ala Pro Asn Cys Pro Leu Tyr 405 410 415 gtc cag ata tta aag cct gaa aat aaa ttt cac atc aaa ttt gct gat 1296 Val Gln Ile Leu Lys Pro Glu Asn Lys Phe His Ile Lys Phe Ala Asp 420 425 430 cat gtt gtt tgt gaa gaa gag ttt aaa tac gcc atg tta gct tta aac 1344 His Val Val Cys Glu Glu Glu Phe Lys Tyr Ala Met Leu Ala Leu Asn 435 440 445 tgt ata tgc cca gca aca tct aca ctt att aca cta ctg gtt cat acc 1392 Cys Ile Cys Pro Ala Thr Ser Thr Leu Ile Thr Leu Leu Val His Thr 450 455 460 tct aga ggg caa gaa ggc cag caa tcg cca gaa caa tgg cag aag atg 1440 Ser Arg Gly Gln Glu Gly Gln Gln Ser Pro Glu Gln Trp Gln Lys Met 465 470 475 480 tac ggt aga tgc tcc ggg aat gaa gtc tac cac att gtt ttg gaa gaa 1488 Tyr Gly Arg Cys Ser Gly Asn Glu Val Tyr His Ile Val Leu Glu Glu 485 490 495 agt aca ttt ttt gct gaa tat gaa gga aag agt ttt aca tat gcc tct 1536 Ser Thr Phe Phe Ala Glu Tyr Glu Gly Lys Ser Phe Thr Tyr Ala Ser 500 505 510 ttc cat gca cac aaa aag ttt ggc gtc tgc ttg att ggt gtt agg agg 1584 Phe His Ala His Lys Lys Phe Gly Val Cys Leu Ile Gly Val Arg Arg 515 520 525 gag gat aat aaa aac att ttg ctg aat cca ggt cct cga tac att atg 1632 Glu Asp Asn Lys Asn Ile Leu Leu Asn Pro Gly Pro Arg Tyr Ile Met 530 535 540 aat tct acg gac ata tgc ttt tat att aat att acc aaa gaa gag aat 1680 Asn Ser Thr Asp Ile Cys Phe Tyr Ile Asn Ile Thr Lys Glu Glu Asn 545 550 555 560 tca gca ttt aaa aac caa gac cag cag aga aaa agc aat gtg tcc agg 1728 Ser Ala Phe Lys Asn Gln Asp Gln Gln Arg Lys Ser Asn Val Ser Arg 565 570 575 tcg ttt tat cat gga cct tcc aga tta cct gta cat agc ata att gcc 1776 Ser Phe Tyr His Gly Pro Ser Arg Leu Pro Val His Ser Ile Ile Ala 580 585 590 agc atg ggt act gtg gct ata gac ctg caa gat aca agc tgt aga tca 1824 Ser Met Gly Thr Val Ala Ile Asp Leu Gln Asp Thr Ser Cys Arg Ser 595 600 605 gca agt ggc cct acc ctg tct ctt cct aca gag gga agc aaa gaa ata 1872 Ala Ser Gly Pro Thr Leu Ser Leu Pro Thr Glu Gly Ser Lys Glu Ile 610 615 620 aga aga cct agc att gct cct gtt tta gag gtt gca gat aca tca tcg 1920 Arg Arg Pro Ser Ile Ala Pro Val Leu Glu Val Ala Asp Thr Ser Ser 625 630 635 640 att caa aca tgt gat ctt cta agt gac caa tca gaa gat gaa act aca 1968 Ile Gln Thr Cys Asp Leu Leu Ser Asp Gln Ser Glu Asp Glu Thr Thr 645 650 655 cca gat gaa gaa atg tct tca aac tta gag tat gct aaa ggt tac cca 2016 Pro Asp Glu Glu Met Ser Ser Asn Leu Glu Tyr Ala Lys Gly Tyr Pro 660 665 670 cct tat tct cca tat ata gga agt tca ccc act ttt tgt cat ctc ctt 2064 Pro Tyr Ser Pro Tyr Ile Gly Ser Ser Pro Thr Phe Cys His Leu Leu 675 680 685 cat gaa aaa gta cca ttt tgc tgc tta aga tta gac aag agt tgc caa 2112 His Glu Lys Val Pro Phe Cys Cys Leu Arg Leu Asp Lys Ser Cys Gln 690 695 700 cat aac tac tat gag gat gca aaa gcc tat gga ttc aaa aat aaa cta 2160 His Asn Tyr Tyr Glu Asp Ala Lys Ala Tyr Gly Phe Lys Asn Lys Leu 705 710 715 720 att ata gtt gca gct gaa aca gct gga aat gga tta tat aac ttt att 2208 Ile Ile Val Ala Ala Glu Thr Ala Gly Asn Gly Leu Tyr Asn Phe Ile 725 730 735 gtt cct ctc agg gca tat tat aga cca aag aaa gaa ctt aat ccc ata 2256 Val Pro Leu Arg Ala Tyr Tyr Arg Pro Lys Lys Glu Leu Asn Pro Ile 740 745 750 gta ctg cta ttg gat aac ccc cta gat gac tta ctc agg tgt gga gtg 2304 Val Leu Leu Leu Asp Asn Pro Leu Asp Asp Leu Leu Arg Cys Gly Val 755 760 765 act ttt gct gct aat atg gtg gtt gtg gat aaa gag agc acc atg agt 2352 Thr Phe Ala Ala Asn Met Val Val Val Asp Lys Glu Ser Thr Met Ser 770 775 780 gcc gag gaa gac tac atg gca gat gcc aaa acc att gtg aac gtg cag 2400 Ala Glu Glu Asp Tyr Met Ala Asp Ala Lys Thr Ile Val Asn Val Gln 785 790 795 800 aca ctc ttc agg ttg ttt tcc agt ctc agt att atc aca gag cta act 2448 Thr Leu Phe Arg Leu Phe Ser Ser Leu Ser Ile Ile Thr Glu Leu Thr 805 810 815 cac ccc gcc aac atg aga ttc atg caa ttc aga gcc aaa gac tgt tac 2496 His Pro Ala Asn Met Arg Phe Met Gln Phe Arg Ala Lys Asp Cys Tyr 820 825 830 tct ctt gct ctt tca aaa ctg gaa aag aaa gaa cgg gag aga ggc tct 2544 Ser Leu Ala Leu Ser Lys Leu Glu Lys Lys Glu Arg Glu Arg Gly Ser 835 840 845 aac ttg gcc ttt atg ttt cga ctg cct ttt gct gct ggg agg gtg ttt 2592 Asn Leu Ala Phe Met Phe Arg Leu Pro Phe Ala Ala Gly Arg Val Phe 850 855 860 agc atc agt atg ttg gac act ctg ctg tat cag tca ttt gtg aag gat 2640 Ser Ile Ser Met Leu Asp Thr Leu Leu Tyr Gln Ser Phe Val Lys Asp 865 870 875 880 tat atg att tct atc acg aga ctt ctg ttg gga ctg gac act aca cca 2688 Tyr Met Ile Ser Ile Thr Arg Leu Leu Leu Gly Leu Asp Thr Thr Pro 885 890 895 gga tct ggg ttt ctt tgt tct atg aaa atc act gca gat gac tta tgg 2736 Gly Ser Gly Phe Leu Cys Ser Met Lys Ile Thr Ala Asp Asp Leu Trp 900 905 910 atc aga act tat gcc aga ctt tat cag aag ttg tgt tct tct act gga 2784 Ile Arg Thr Tyr Ala Arg Leu Tyr Gln Lys Leu Cys Ser Ser Thr Gly 915 920 925 gat gtt ccc att gga atc tac agg act gag tct cag aaa ctt act aca 2832 Asp Val Pro Ile Gly Ile Tyr Arg Thr Glu Ser Gln Lys Leu Thr Thr 930 935 940 tct gag tct cga aaa ata gca tca caa tct caa ata tct atc agt gta 2880 Ser Glu Ser Arg Lys Ile Ala Ser Gln Ser Gln Ile Ser Ile Ser Val 945 950 955 960 gaa gag tgg gaa gac acc aaa gac tcc aaa gaa caa ggg cac cac cgc 2928 Glu Glu Trp Glu Asp Thr Lys Asp Ser Lys Glu Gln Gly His His Arg 965 970 975 agc aac cac cgc aac tca aca tcc agt gac cag tcg gac cat ccc ttg 2976 Ser Asn His Arg Asn Ser Thr Ser Ser Asp Gln Ser Asp His Pro Leu 980 985 990 ctg cgg aga aaa agc atg cag tgg gcc cga aga ctg agc aga aaa ggc 3024 Leu Arg Arg Lys Ser Met Gln Trp Ala Arg Arg Leu Ser Arg Lys Gly 995 1000 1005 cca aaa cac tct ggt aaa aca gct gaa aaa ata acc cag cag cga ctg 3072 Pro Lys His Ser Gly Lys Thr Ala Glu Lys Ile Thr Gln Gln Arg Leu 1010 1015 1020 aac ctc tac agg agg tca gaa aga caa gag ctt gct gaa ctt gtg aaa 3120 Asn Leu Tyr Arg Arg Ser Glu Arg Gln Glu Leu Ala Glu Leu Val Lys 1025 1030 1035 1040 aat aga atg aaa cac ttg ggt ctt tct aca gtg gga tat gat gaa atg 3168 Asn Arg Met Lys His Leu Gly Leu Ser Thr Val Gly Tyr Asp Glu Met 1045 1050 1055 aat gat cat caa agt acc ctc tcc tac atc ctg att aac cca tct cca 3216 Asn Asp His Gln Ser Thr Leu Ser Tyr Ile Leu Ile Asn Pro Ser Pro 1060 1065 1070 gat acc aga ata gag ctg aat gat gtt gta tac tta att cga cca gat 3264 Asp Thr Arg Ile Glu Leu Asn Asp Val Val Tyr Leu Ile Arg Pro Asp 1075 1080 1085 cca ctg gcc tac ctt cca aac agt gag ccc agt cga aga aac agc atc 3312 Pro Leu Ala Tyr Leu Pro Asn Ser Glu Pro Ser Arg Arg Asn Ser Ile 1090 1095 1100 tgc aat gtc act ggt caa gat tct cgg gag gaa act caa ctt tga 3357 Cys Asn Val Thr Gly Gln Asp Ser Arg Glu Glu Thr Gln Leu * 1105 1110 1115 <210> SEQ ID NO 10 <211> LENGTH: 2847 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (561)...(2477) <400> SEQUENCE: 10 ccacgcgtcc ggccctgtgc ttcggatggc ggcgggaggt tgatggcgag tggtgctgaa 60 gggacagctc cagcagtggc tgatttgggg gagaaacaaa atctgcagat ggaatccgag 120 cagggcgact tcaccttcaa gtggtgagct ctcctgacct gcggccagtc tccactccat 180 tcacggccag ccgatctgcc cgctcccgga ggggtcgggc agtgccggct ggacccgccc 240 cgagctccat ggtttgccca accctgcgcg atggtgactc tgggcgcgga ggttggcgac 300 tggcaaatcc gcagatcaca gaatgaaggc ggggagcgcg gccggcggcc ggcgggggct 360 ttctccccca ccccagcgcc cagggaagcg gctcaaccac ctgaatccgg aaaacgccaa 420 caagtagttt ctcgtcggag aagggcggct cacctgggcg ccaagactca gtcccgctgc 480 ccagagaacc tcgtccactc ggaaaccaaa gcagaaccac ttttctctcg gtctcgttaa 540 gtcatgtctg agtcacagag atg ggc aag atc gag aac aac gag agg gtg atc 593 Met Gly Lys Ile Glu Asn Asn Glu Arg Val Ile 1 5 10 ctc aat gtc ggg ggc acc cgg cac gaa acc tac cgc agc acc ctc aag 641 Leu Asn Val Gly Gly Thr Arg His Glu Thr Tyr Arg Ser Thr Leu Lys 15 20 25 acc ctg cct gga aca cgc ctg gcc ctt ctt gcc tcc tcc gag ccc cca 689 Thr Leu Pro Gly Thr Arg Leu Ala Leu Leu Ala Ser Ser Glu Pro Pro 30 35 40 ggc gac tgc ttg acc acg gcg ggc gac aag ctg cag ccg tcg ccg cct 737 Gly Asp Cys Leu Thr Thr Ala Gly Asp Lys Leu Gln Pro Ser Pro Pro 45 50 55 cca ctg tcg ccg ccg ccg aga gcg ccc ccg ctg tcc ccc ggg cca ggc 785 Pro Leu Ser Pro Pro Pro Arg Ala Pro Pro Leu Ser Pro Gly Pro Gly 60 65 70 75 ggc tgc ttc gag ggc ggc gcg ggc aac tgc agt tcc cgc ggc ggc agg 833 Gly Cys Phe Glu Gly Gly Ala Gly Asn Cys Ser Ser Arg Gly Gly Arg 80 85 90 gcc agc gac cat ccc ggt ggc ggc cgc gag ttc ttc ttc gac cgg cac 881 Ala Ser Asp His Pro Gly Gly Gly Arg Glu Phe Phe Phe Asp Arg His 95 100 105 ccg ggc gtc ttc gcc tat gtg ctc aat tac tac cgc acc ggc aag ctg 929 Pro Gly Val Phe Ala Tyr Val Leu Asn Tyr Tyr Arg Thr Gly Lys Leu 110 115 120 cac tgc ccc gca gac gtg tgc ggg ccg ctc ttc gag gag gag ctg gcc 977 His Cys Pro Ala Asp Val Cys Gly Pro Leu Phe Glu Glu Glu Leu Ala 125 130 135 ttc tgg ggc atc gac gag acc gac gtg gag ccc tgc tgc tgg atg acc 1025 Phe Trp Gly Ile Asp Glu Thr Asp Val Glu Pro Cys Cys Trp Met Thr 140 145 150 155 tac cgg cag cac cgc gac gcc gag gag gcg ctg gac atc ttc gag acc 1073 Tyr Arg Gln His Arg Asp Ala Glu Glu Ala Leu Asp Ile Phe Glu Thr 160 165 170 ccc gac ctc att ggc ggc gac ccc ggc gac gac gag gac ctg gcg gcc 1121 Pro Asp Leu Ile Gly Gly Asp Pro Gly Asp Asp Glu Asp Leu Ala Ala 175 180 185 aag agg ctg ggc atc gag gac gcg gcg ggg ctc ggg ggc ccc gac ggc 1169 Lys Arg Leu Gly Ile Glu Asp Ala Ala Gly Leu Gly Gly Pro Asp Gly 190 195 200 aaa tct ggc cgc tgg agg agg ctg cag ccc cgc atg tgg gcc ctc ttc 1217 Lys Ser Gly Arg Trp Arg Arg Leu Gln Pro Arg Met Trp Ala Leu Phe 205 210 215 gaa gac ccc tac tcg tcc aga gcc gcc agg ttt att gct ttt gct tct 1265 Glu Asp Pro Tyr Ser Ser Arg Ala Ala Arg Phe Ile Ala Phe Ala Ser 220 225 230 235 tta ttc ttc atc ctg gtt tca att aca act ttt tgc ctg gaa aca cat 1313 Leu Phe Phe Ile Leu Val Ser Ile Thr Thr Phe Cys Leu Glu Thr His 240 245 250 gaa gct ttc aat att gtt aaa aac aag aca gaa cca gtc atc aat ggc 1361 Glu Ala Phe Asn Ile Val Lys Asn Lys Thr Glu Pro Val Ile Asn Gly 255 260 265 aca agt gtt gtt cta cag tat gaa att gaa acg gat cct gcc ttg acg 1409 Thr Ser Val Val Leu Gln Tyr Glu Ile Glu Thr Asp Pro Ala Leu Thr 270 275 280 tat gta gaa gga gtg tgt gtg gtg tgg ttt act ttt gaa ttt tta gtc 1457 Tyr Val Glu Gly Val Cys Val Val Trp Phe Thr Phe Glu Phe Leu Val 285 290 295 cgt att gtt ttt tca ccc aat aaa ctt gaa ttc atc aaa aat ctc ttg 1505 Arg Ile Val Phe Ser Pro Asn Lys Leu Glu Phe Ile Lys Asn Leu Leu 300 305 310 315 aat atc att gac ttt gtg gcc atc cta cct ttc tac tta gag gtg gga 1553 Asn Ile Ile Asp Phe Val Ala Ile Leu Pro Phe Tyr Leu Glu Val Gly 320 325 330 ctc agt ggg ctg tca tcc aaa gct gct aaa gat gtg ctt ggc ttc ctc 1601 Leu Ser Gly Leu Ser Ser Lys Ala Ala Lys Asp Val Leu Gly Phe Leu 335 340 345 agg gtg gta agg ttt gtg agg atc ctg aga att ttc aag ctc acc cgc 1649 Arg Val Val Arg Phe Val Arg Ile Leu Arg Ile Phe Lys Leu Thr Arg 350 355 360 cat ttt gta ggt ctg agg gtg ctt gga cat act ctt cga gct agt act 1697 His Phe Val Gly Leu Arg Val Leu Gly His Thr Leu Arg Ala Ser Thr 365 370 375 aat gaa ttt ttg ctg ctg ata att ttc ctg gct cta gga gtt ttg ata 1745 Asn Glu Phe Leu Leu Leu Ile Ile Phe Leu Ala Leu Gly Val Leu Ile 380 385 390 395 ttt gct acc atg atc tac tat gcc gag aga gtg gga gct caa cct aac 1793 Phe Ala Thr Met Ile Tyr Tyr Ala Glu Arg Val Gly Ala Gln Pro Asn 400 405 410 gac cct tca gct agt gag cac aca cag ttc aaa aac att ccc att ggg 1841 Asp Pro Ser Ala Ser Glu His Thr Gln Phe Lys Asn Ile Pro Ile Gly 415 420 425 ttc tgg tgg gct gta gtg acc atg act acc ctg ggt tat ggg gat atg 1889 Phe Trp Trp Ala Val Val Thr Met Thr Thr Leu Gly Tyr Gly Asp Met 430 435 440 tac ccc caa aca tgg tca ggc atg ctg gtg gga gcc ctg tgt gct ctg 1937 Tyr Pro Gln Thr Trp Ser Gly Met Leu Val Gly Ala Leu Cys Ala Leu 445 450 455 gct gga gtg ctg aca ata gcc atg cca gtg cct gtc att gtc aat aat 1985 Ala Gly Val Leu Thr Ile Ala Met Pro Val Pro Val Ile Val Asn Asn 460 465 470 475 ttt gga atg tac tac tcc ttg gca atg gca aag cag aaa ctt cca agg 2033 Phe Gly Met Tyr Tyr Ser Leu Ala Met Ala Lys Gln Lys Leu Pro Arg 480 485 490 aaa aga aag aag cac atc cct cct gct cct cag gca agc tca cct act 2081 Lys Arg Lys Lys His Ile Pro Pro Ala Pro Gln Ala Ser Ser Pro Thr 495 500 505 ttt tgc aag aca gaa tta aat atg gcc tgc aat agt aca cag agt gac 2129 Phe Cys Lys Thr Glu Leu Asn Met Ala Cys Asn Ser Thr Gln Ser Asp 510 515 520 aca tgt ctg ggc aaa gac aat cga ctt ctg gaa cat aac aga tca gtg 2177 Thr Cys Leu Gly Lys Asp Asn Arg Leu Leu Glu His Asn Arg Ser Val 525 530 535 tta tca ggt gac gac agt aca gga agt gag ccg cca cta tca ccc cca 2225 Leu Ser Gly Asp Asp Ser Thr Gly Ser Glu Pro Pro Leu Ser Pro Pro 540 545 550 555 gaa agg ctc ccc atc aga cgc tct agt acc aga gac aaa aac aga aga 2273 Glu Arg Leu Pro Ile Arg Arg Ser Ser Thr Arg Asp Lys Asn Arg Arg 560 565 570 ggg gaa aca tgt ttc cta ctg acg aca ggt gat tac acg tgt gct tct 2321 Gly Glu Thr Cys Phe Leu Leu Thr Thr Gly Asp Tyr Thr Cys Ala Ser 575 580 585 gat gga ggg atc agg aaa gga tat gaa aaa tcc cga agc tta aac aac 2369 Asp Gly Gly Ile Arg Lys Gly Tyr Glu Lys Ser Arg Ser Leu Asn Asn 590 595 600 ata gcg ggc ttg gca ggc aat gct ctg agg ctc tct cca gta aca tca 2417 Ile Ala Gly Leu Ala Gly Asn Ala Leu Arg Leu Ser Pro Val Thr Ser 605 610 615 ccc tac aac tct cct tgt cct ctg agg cgc tct cga tct ccc atc cca 2465 Pro Tyr Asn Ser Pro Cys Pro Leu Arg Arg Ser Arg Ser Pro Ile Pro 620 625 630 635 tct atc ttg taa accaaacaac caaactgcat cagtcggcta aattgtatta 2517 Ser Ile Leu * attcaagygc tgtttacccc ataatggaaa taattaaatg tagagttact ccaggctcca 2577 ttaatacagt ataaatcttg cgtgatacta caatttgaag tcagaaatgc cacttgggta 2637 gctaatgaat cttacccagg ctttaaagat tgtctaaagt agtgctaaga tccctcctat 2697 taattgccct gatatccttt tgcaataaaa tgacagatag tgtcagatat tgaccagtgc 2757 actaatatat aaacataccc tcagggagat atatttaaaa cagtgtgctt ccaaatgcca 2817 accacttcat tggaacttta tttcttgtga 2847 <210> SEQ ID NO 11 <211> LENGTH: 638 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 11 Met Gly Lys Ile Glu Asn Asn Glu Arg Val Ile Leu Asn Val Gly Gly 1 5 10 15 Thr Arg His Glu Thr Tyr Arg Ser Thr Leu Lys Thr Leu Pro Gly Thr 20 25 30 Arg Leu Ala Leu Leu Ala Ser Ser Glu Pro Pro Gly Asp Cys Leu Thr 35 40 45 Thr Ala Gly Asp Lys Leu Gln Pro Ser Pro Pro Pro Leu Ser Pro Pro 50 55 60 Pro Arg Ala Pro Pro Leu Ser Pro Gly Pro Gly Gly Cys Phe Glu Gly 65 70 75 80 Gly Ala Gly Asn Cys Ser Ser Arg Gly Gly Arg Ala Ser Asp His Pro 85 90 95 Gly Gly Gly Arg Glu Phe Phe Phe Asp Arg His Pro Gly Val Phe Ala 100 105 110 Tyr Val Leu Asn Tyr Tyr Arg Thr Gly Lys Leu His Cys Pro Ala Asp 115 120 125 Val Cys Gly Pro Leu Phe Glu Glu Glu Leu Ala Phe Trp Gly Ile Asp 130 135 140 Glu Thr Asp Val Glu Pro Cys Cys Trp Met Thr Tyr Arg Gln His Arg 145 150 155 160 Asp Ala Glu Glu Ala Leu Asp Ile Phe Glu Thr Pro Asp Leu Ile Gly 165 170 175 Gly Asp Pro Gly Asp Asp Glu Asp Leu Ala Ala Lys Arg Leu Gly Ile 180 185 190 Glu Asp Ala Ala Gly Leu Gly Gly Pro Asp Gly Lys Ser Gly Arg Trp 195 200 205 Arg Arg Leu Gln Pro Arg Met Trp Ala Leu Phe Glu Asp Pro Tyr Ser 210 215 220 Ser Arg Ala Ala Arg Phe Ile Ala Phe Ala Ser Leu Phe Phe Ile Leu 225 230 235 240 Val Ser Ile Thr Thr Phe Cys Leu Glu Thr His Glu Ala Phe Asn Ile 245 250 255 Val Lys Asn Lys Thr Glu Pro Val Ile Asn Gly Thr Ser Val Val Leu 260 265 270 Gln Tyr Glu Ile Glu Thr Asp Pro Ala Leu Thr Tyr Val Glu Gly Val 275 280 285 Cys Val Val Trp Phe Thr Phe Glu Phe Leu Val Arg Ile Val Phe Ser 290 295 300 Pro Asn Lys Leu Glu Phe Ile Lys Asn Leu Leu Asn Ile Ile Asp Phe 305 310 315 320 Val Ala Ile Leu Pro Phe Tyr Leu Glu Val Gly Leu Ser Gly Leu Ser 325 330 335 Ser Lys Ala Ala Lys Asp Val Leu Gly Phe Leu Arg Val Val Arg Phe 340 345 350 Val Arg Ile Leu Arg Ile Phe Lys Leu Thr Arg His Phe Val Gly Leu 355 360 365 Arg Val Leu Gly His Thr Leu Arg Ala Ser Thr Asn Glu Phe Leu Leu 370 375 380 Leu Ile Ile Phe Leu Ala Leu Gly Val Leu Ile Phe Ala Thr Met Ile 385 390 395 400 Tyr Tyr Ala Glu Arg Val Gly Ala Gln Pro Asn Asp Pro Ser Ala Ser 405 410 415 Glu His Thr Gln Phe Lys Asn Ile Pro Ile Gly Phe Trp Trp Ala Val 420 425 430 Val Thr Met Thr Thr Leu Gly Tyr Gly Asp Met Tyr Pro Gln Thr Trp 435 440 445 Ser Gly Met Leu Val Gly Ala Leu Cys Ala Leu Ala Gly Val Leu Thr 450 455 460 Ile Ala Met Pro Val Pro Val Ile Val Asn Asn Phe Gly Met Tyr Tyr 465 470 475 480 Ser Leu Ala Met Ala Lys Gln Lys Leu Pro Arg Lys Arg Lys Lys His 485 490 495 Ile Pro Pro Ala Pro Gln Ala Ser Ser Pro Thr Phe Cys Lys Thr Glu 500 505 510 Leu Asn Met Ala Cys Asn Ser Thr Gln Ser Asp Thr Cys Leu Gly Lys 515 520 525 Asp Asn Arg Leu Leu Glu His Asn Arg Ser Val Leu Ser Gly Asp Asp 530 535 540 Ser Thr Gly Ser Glu Pro Pro Leu Ser Pro Pro Glu Arg Leu Pro Ile 545 550 555 560 Arg Arg Ser Ser Thr Arg Asp Lys Asn Arg Arg Gly Glu Thr Cys Phe 565 570 575 Leu Leu Thr Thr Gly Asp Tyr Thr Cys Ala Ser Asp Gly Gly Ile Arg 580 585 590 Lys Gly Tyr Glu Lys Ser Arg Ser Leu Asn Asn Ile Ala Gly Leu Ala 595 600 605 Gly Asn Ala Leu Arg Leu Ser Pro Val Thr Ser Pro Tyr Asn Ser Pro 610 615 620 Cys Pro Leu Arg Arg Ser Arg Ser Pro Ile Pro Ser Ile Leu 625 630 635 <210> SEQ ID NO 12 <211> LENGTH: 1917 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(1917) <400> SEQUENCE: 12 atg ggc aag atc gag aac aac gag agg gtg atc ctc aat gtc ggg ggc 48 Met Gly Lys Ile Glu Asn Asn Glu Arg Val Ile Leu Asn Val Gly Gly 1 5 10 15 acc cgg cac gaa acc tac cgc agc acc ctc aag acc ctg cct gga aca 96 Thr Arg His Glu Thr Tyr Arg Ser Thr Leu Lys Thr Leu Pro Gly Thr 20 25 30 cgc ctg gcc ctt ctt gcc tcc tcc gag ccc cca ggc gac tgc ttg acc 144 Arg Leu Ala Leu Leu Ala Ser Ser Glu Pro Pro Gly Asp Cys Leu Thr 35 40 45 acg gcg ggc gac aag ctg cag ccg tcg ccg cct cca ctg tcg ccg ccg 192 Thr Ala Gly Asp Lys Leu Gln Pro Ser Pro Pro Pro Leu Ser Pro Pro 50 55 60 ccg aga gcg ccc ccg ctg tcc ccc ggg cca ggc ggc tgc ttc gag ggc 240 Pro Arg Ala Pro Pro Leu Ser Pro Gly Pro Gly Gly Cys Phe Glu Gly 65 70 75 80 ggc gcg ggc aac tgc agt tcc cgc ggc ggc agg gcc agc gac cat ccc 288 Gly Ala Gly Asn Cys Ser Ser Arg Gly Gly Arg Ala Ser Asp His Pro 85 90 95 ggt ggc ggc cgc gag ttc ttc ttc gac cgg cac ccg ggc gtc ttc gcc 336 Gly Gly Gly Arg Glu Phe Phe Phe Asp Arg His Pro Gly Val Phe Ala 100 105 110 tat gtg ctc aat tac tac cgc acc ggc aag ctg cac tgc ccc gca gac 384 Tyr Val Leu Asn Tyr Tyr Arg Thr Gly Lys Leu His Cys Pro Ala Asp 115 120 125 gtg tgc ggg ccg ctc ttc gag gag gag ctg gcc ttc tgg ggc atc gac 432 Val Cys Gly Pro Leu Phe Glu Glu Glu Leu Ala Phe Trp Gly Ile Asp 130 135 140 gag acc gac gtg gag ccc tgc tgc tgg atg acc tac cgg cag cac cgc 480 Glu Thr Asp Val Glu Pro Cys Cys Trp Met Thr Tyr Arg Gln His Arg 145 150 155 160 gac gcc gag gag gcg ctg gac atc ttc gag acc ccc gac ctc att ggc 528 Asp Ala Glu Glu Ala Leu Asp Ile Phe Glu Thr Pro Asp Leu Ile Gly 165 170 175 ggc gac ccc ggc gac gac gag gac ctg gcg gcc aag agg ctg ggc atc 576 Gly Asp Pro Gly Asp Asp Glu Asp Leu Ala Ala Lys Arg Leu Gly Ile 180 185 190 gag gac gcg gcg ggg ctc ggg ggc ccc gac ggc aaa tct ggc cgc tgg 624 Glu Asp Ala Ala Gly Leu Gly Gly Pro Asp Gly Lys Ser Gly Arg Trp 195 200 205 agg agg ctg cag ccc cgc atg tgg gcc ctc ttc gaa gac ccc tac tcg 672 Arg Arg Leu Gln Pro Arg Met Trp Ala Leu Phe Glu Asp Pro Tyr Ser 210 215 220 tcc aga gcc gcc agg ttt att gct ttt gct tct tta ttc ttc atc ctg 720 Ser Arg Ala Ala Arg Phe Ile Ala Phe Ala Ser Leu Phe Phe Ile Leu 225 230 235 240 gtt tca att aca act ttt tgc ctg gaa aca cat gaa gct ttc aat att 768 Val Ser Ile Thr Thr Phe Cys Leu Glu Thr His Glu Ala Phe Asn Ile 245 250 255 gtt aaa aac aag aca gaa cca gtc atc aat ggc aca agt gtt gtt cta 816 Val Lys Asn Lys Thr Glu Pro Val Ile Asn Gly Thr Ser Val Val Leu 260 265 270 cag tat gaa att gaa acg gat cct gcc ttg acg tat gta gaa gga gtg 864 Gln Tyr Glu Ile Glu Thr Asp Pro Ala Leu Thr Tyr Val Glu Gly Val 275 280 285 tgt gtg gtg tgg ttt act ttt gaa ttt tta gtc cgt att gtt ttt tca 912 Cys Val Val Trp Phe Thr Phe Glu Phe Leu Val Arg Ile Val Phe Ser 290 295 300 ccc aat aaa ctt gaa ttc atc aaa aat ctc ttg aat atc att gac ttt 960 Pro Asn Lys Leu Glu Phe Ile Lys Asn Leu Leu Asn Ile Ile Asp Phe 305 310 315 320 gtg gcc atc cta cct ttc tac tta gag gtg gga ctc agt ggg ctg tca 1008 Val Ala Ile Leu Pro Phe Tyr Leu Glu Val Gly Leu Ser Gly Leu Ser 325 330 335 tcc aaa gct gct aaa gat gtg ctt ggc ttc ctc agg gtg gta agg ttt 1056 Ser Lys Ala Ala Lys Asp Val Leu Gly Phe Leu Arg Val Val Arg Phe 340 345 350 gtg agg atc ctg aga att ttc aag ctc acc cgc cat ttt gta ggt ctg 1104 Val Arg Ile Leu Arg Ile Phe Lys Leu Thr Arg His Phe Val Gly Leu 355 360 365 agg gtg ctt gga cat act ctt cga gct agt act aat gaa ttt ttg ctg 1152 Arg Val Leu Gly His Thr Leu Arg Ala Ser Thr Asn Glu Phe Leu Leu 370 375 380 ctg ata att ttc ctg gct cta gga gtt ttg ata ttt gct acc atg atc 1200 Leu Ile Ile Phe Leu Ala Leu Gly Val Leu Ile Phe Ala Thr Met Ile 385 390 395 400 tac tat gcc gag aga gtg gga gct caa cct aac gac cct tca gct agt 1248 Tyr Tyr Ala Glu Arg Val Gly Ala Gln Pro Asn Asp Pro Ser Ala Ser 405 410 415 gag cac aca cag ttc aaa aac att ccc att ggg ttc tgg tgg gct gta 1296 Glu His Thr Gln Phe Lys Asn Ile Pro Ile Gly Phe Trp Trp Ala Val 420 425 430 gtg acc atg act acc ctg ggt tat ggg gat atg tac ccc caa aca tgg 1344 Val Thr Met Thr Thr Leu Gly Tyr Gly Asp Met Tyr Pro Gln Thr Trp 435 440 445 tca ggc atg ctg gtg gga gcc ctg tgt gct ctg gct gga gtg ctg aca 1392 Ser Gly Met Leu Val Gly Ala Leu Cys Ala Leu Ala Gly Val Leu Thr 450 455 460 ata gcc atg cca gtg cct gtc att gtc aat aat ttt gga atg tac tac 1440 Ile Ala Met Pro Val Pro Val Ile Val Asn Asn Phe Gly Met Tyr Tyr 465 470 475 480 tcc ttg gca atg gca aag cag aaa ctt cca agg aaa aga aag aag cac 1488 Ser Leu Ala Met Ala Lys Gln Lys Leu Pro Arg Lys Arg Lys Lys His 485 490 495 atc cct cct gct cct cag gca agc tca cct act ttt tgc aag aca gaa 1536 Ile Pro Pro Ala Pro Gln Ala Ser Ser Pro Thr Phe Cys Lys Thr Glu 500 505 510 tta aat atg gcc tgc aat agt aca cag agt gac aca tgt ctg ggc aaa 1584 Leu Asn Met Ala Cys Asn Ser Thr Gln Ser Asp Thr Cys Leu Gly Lys 515 520 525 gac aat cga ctt ctg gaa cat aac aga tca gtg tta tca ggt gac gac 1632 Asp Asn Arg Leu Leu Glu His Asn Arg Ser Val Leu Ser Gly Asp Asp 530 535 540 agt aca gga agt gag ccg cca cta tca ccc cca gaa agg ctc ccc atc 1680 Ser Thr Gly Ser Glu Pro Pro Leu Ser Pro Pro Glu Arg Leu Pro Ile 545 550 555 560 aga cgc tct agt acc aga gac aaa aac aga aga ggg gaa aca tgt ttc 1728 Arg Arg Ser Ser Thr Arg Asp Lys Asn Arg Arg Gly Glu Thr Cys Phe 565 570 575 cta ctg acg aca ggt gat tac acg tgt gct tct gat gga ggg atc agg 1776 Leu Leu Thr Thr Gly Asp Tyr Thr Cys Ala Ser Asp Gly Gly Ile Arg 580 585 590 aaa gga tat gaa aaa tcc cga agc tta aac aac ata gcg ggc ttg gca 1824 Lys Gly Tyr Glu Lys Ser Arg Ser Leu Asn Asn Ile Ala Gly Leu Ala 595 600 605 ggc aat gct ctg agg ctc tct cca gta aca tca ccc tac aac tct cct 1872 Gly Asn Ala Leu Arg Leu Ser Pro Val Thr Ser Pro Tyr Asn Ser Pro 610 615 620 tgt cct ctg agg cgc tct cga tct ccc atc cca tct atc ttg taa 1917 Cys Pro Leu Arg Arg Ser Arg Ser Pro Ile Pro Ser Ile Leu * 625 630 635 <210> SEQ ID NO 13 <211> LENGTH: 6582 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (524)...(3913) <400> SEQUENCE: 13 ccacgcgtcc gcccacgcgt ccgcccacgc gtccgagaag gcttaggtgg gcaggcagga 60 cgagagaaag actgagagga gggaaagccg cgtaggtggg agtacagcgg cgcgagggtc 120 gagggggaac cctcgtcggt gcagatgagg agggtgggct ttcagaacta gtcccccctc 180 gcaccccgcc ccgcccctcc cgcgctgggg tcttcacggt gccctgcctc agagcccggc 240 tccaccacgc ccggaagagg gagtctggcc gtcggctggc tcagggcggg ccggttggct 300 gtacccaggc tccctggccc gagtgcggga ccagagcgcg gggcggcgcg gcagccgcgg 360 gccgaggagg ggctgcgagc gaaacggcgc ggcgcggcac ggcggacgag ttagggccgg 420 ggcgagggag gctgtggctc ccgacagaga caggggagta gtgtcgggct gaggcgagac 480 agcccggtag agcccagctc agcgcccggc agccttcgac gcg atg ttc cgc cgg 535 Met Phe Arg Arg 1 agc ttg aat cgt ttt tgt gct gga gaa gag aaa cga gtt ggc aca cgc 583 Ser Leu Asn Arg Phe Cys Ala Gly Glu Glu Lys Arg Val Gly Thr Arg 5 10 15 20 aca gtg ttt gtt ggc aat cat cca gtt tcg gaa aca gaa gct tac att 631 Thr Val Phe Val Gly Asn His Pro Val Ser Glu Thr Glu Ala Tyr Ile 25 30 35 gca caa aga ttt tgt gat aat aga ata gtc tca tct aag tat aca ctt 679 Ala Gln Arg Phe Cys Asp Asn Arg Ile Val Ser Ser Lys Tyr Thr Leu 40 45 50 tgg aat ttt ctc cca aag aat ctg ttt gaa cag ttt aga aga att gca 727 Trp Asn Phe Leu Pro Lys Asn Leu Phe Glu Gln Phe Arg Arg Ile Ala 55 60 65 aat ttt tat ttt ctc ata atc ttc ctt gta cag gtc aca gta gac aca 775 Asn Phe Tyr Phe Leu Ile Ile Phe Leu Val Gln Val Thr Val Asp Thr 70 75 80 cca act agc cca gtt acc agt gga ctt cca ctt ttc ttt gtt ata act 823 Pro Thr Ser Pro Val Thr Ser Gly Leu Pro Leu Phe Phe Val Ile Thr 85 90 95 100 gtt aca gcc atc aag cag gga tat gag gat tgg ctg aga cac aga gct 871 Val Thr Ala Ile Lys Gln Gly Tyr Glu Asp Trp Leu Arg His Arg Ala 105 110 115 gac aat gaa gtc aac aaa agc act gtt tac att att gaa aat gca aag 919 Asp Asn Glu Val Asn Lys Ser Thr Val Tyr Ile Ile Glu Asn Ala Lys 120 125 130 cga gtg aga aaa gaa agt gaa aaa atc aag gtt ggt gat gta gta gaa 967 Arg Val Arg Lys Glu Ser Glu Lys Ile Lys Val Gly Asp Val Val Glu 135 140 145 gta cag gca gat gaa acc ttt ccc tgt gat ctt att ctt cta tca tct 1015 Val Gln Ala Asp Glu Thr Phe Pro Cys Asp Leu Ile Leu Leu Ser Ser 150 155 160 tgc acc act gat gga acc tgt tat gtc act aca gcc agt ctt gat ggg 1063 Cys Thr Thr Asp Gly Thr Cys Tyr Val Thr Thr Ala Ser Leu Asp Gly 165 170 175 180 gaa tcc aat tgc aag aca cat tat gca gta cgt gat acc att gca ctg 1111 Glu Ser Asn Cys Lys Thr His Tyr Ala Val Arg Asp Thr Ile Ala Leu 185 190 195 tgt aca gca gaa tcc atc gat acc ctc cga gca gca att gaa tgt gaa 1159 Cys Thr Ala Glu Ser Ile Asp Thr Leu Arg Ala Ala Ile Glu Cys Glu 200 205 210 cag cct caa cct gac ctc tac aaa ttt gtt ggg cga atc aat atc tac 1207 Gln Pro Gln Pro Asp Leu Tyr Lys Phe Val Gly Arg Ile Asn Ile Tyr 215 220 225 agt aat agt ctt gag gct gtt gcc agg tct ttg gga cct gaa aat ctc 1255 Ser Asn Ser Leu Glu Ala Val Ala Arg Ser Leu Gly Pro Glu Asn Leu 230 235 240 ttg ctg aaa gga gct acg cta aaa aat acc gag aag ata tat gga gtt 1303 Leu Leu Lys Gly Ala Thr Leu Lys Asn Thr Glu Lys Ile Tyr Gly Val 245 250 255 260 gct gtt tac act gga atg gaa acc aaa atg gct ttg aac tac caa ggg 1351 Ala Val Tyr Thr Gly Met Glu Thr Lys Met Ala Leu Asn Tyr Gln Gly 265 270 275 aaa tct cag aaa cgt tct gct gtt gaa aaa tct att aat gct ttc ctg 1399 Lys Ser Gln Lys Arg Ser Ala Val Glu Lys Ser Ile Asn Ala Phe Leu 280 285 290 att gta tat tta ttt atc tta ctg acc aaa gct gca gta tgc act act 1447 Ile Val Tyr Leu Phe Ile Leu Leu Thr Lys Ala Ala Val Cys Thr Thr 295 300 305 cta aag tat gtt tgg caa agt acc cca tac aat gat gaa cct tgg tat 1495 Leu Lys Tyr Val Trp Gln Ser Thr Pro Tyr Asn Asp Glu Pro Trp Tyr 310 315 320 aac caa aag act cag aaa gag cga gag acc ttg aag gtt tta aaa atg 1543 Asn Gln Lys Thr Gln Lys Glu Arg Glu Thr Leu Lys Val Leu Lys Met 325 330 335 340 ttc acc gac ttc cta tca ttt atg gtt cta ttc aac ttt atc att cct 1591 Phe Thr Asp Phe Leu Ser Phe Met Val Leu Phe Asn Phe Ile Ile Pro 345 350 355 gtc tcc atg tac gtc aca gta gaa atg cag aaa ttc ttg ggc tcc ttc 1639 Val Ser Met Tyr Val Thr Val Glu Met Gln Lys Phe Leu Gly Ser Phe 360 365 370 ttc atc tca tgg gat aag gac ttt tat gat gaa gaa att aat gaa gga 1687 Phe Ile Ser Trp Asp Lys Asp Phe Tyr Asp Glu Glu Ile Asn Glu Gly 375 380 385 gcc ctg gtt aac aca tca gac ctt aat gaa gaa ctt ggt cag gtg gat 1735 Ala Leu Val Asn Thr Ser Asp Leu Asn Glu Glu Leu Gly Gln Val Asp 390 395 400 tat gta ttt aca gat aag act gga aca ctc act gaa aac agc atg gaa 1783 Tyr Val Phe Thr Asp Lys Thr Gly Thr Leu Thr Glu Asn Ser Met Glu 405 410 415 420 ttc att gaa tgc tgc ata gat ggc cac aaa tat aaa ggt gta act caa 1831 Phe Ile Glu Cys Cys Ile Asp Gly His Lys Tyr Lys Gly Val Thr Gln 425 430 435 gag gtt gat gga tta tct caa act gat gga act tta aca tat ttt gac 1879 Glu Val Asp Gly Leu Ser Gln Thr Asp Gly Thr Leu Thr Tyr Phe Asp 440 445 450 aaa gta gat aag aat cga gaa gag ctg ttt cta cgt gcc ttg tgt tta 1927 Lys Val Asp Lys Asn Arg Glu Glu Leu Phe Leu Arg Ala Leu Cys Leu 455 460 465 tgt cat act gta gaa atc aaa aca aac gat gct gtt gat gga gct aca 1975 Cys His Thr Val Glu Ile Lys Thr Asn Asp Ala Val Asp Gly Ala Thr 470 475 480 gaa tca gct gaa tta acc tat atc tcc tct tca cca gat gaa ata gct 2023 Glu Ser Ala Glu Leu Thr Tyr Ile Ser Ser Ser Pro Asp Glu Ile Ala 485 490 495 500 ttg gtg aaa gga gct aaa agg tac ggg ttc aca ttt tta gga aat cga 2071 Leu Val Lys Gly Ala Lys Arg Tyr Gly Phe Thr Phe Leu Gly Asn Arg 505 510 515 aat gga tat atg aga gta gag aac caa aga aaa gaa ata gaa gaa tat 2119 Asn Gly Tyr Met Arg Val Glu Asn Gln Arg Lys Glu Ile Glu Glu Tyr 520 525 530 gaa ctt ctt cac acc tta aac ttt gat gct gtc cgg cga cgt atg agt 2167 Glu Leu Leu His Thr Leu Asn Phe Asp Ala Val Arg Arg Arg Met Ser 535 540 545 gta att gtg aag act caa gaa gga gac ata ctt ctc ttt tgt aaa gga 2215 Val Ile Val Lys Thr Gln Glu Gly Asp Ile Leu Leu Phe Cys Lys Gly 550 555 560 gca gac tcg gca gtt ttt ccc aga gtg caa aat cat gaa att gag tta 2263 Ala Asp Ser Ala Val Phe Pro Arg Val Gln Asn His Glu Ile Glu Leu 565 570 575 580 act aaa gtc cat gtg gaa cgt aat gca atg gat ggg tat cgg aca ctc 2311 Thr Lys Val His Val Glu Arg Asn Ala Met Asp Gly Tyr Arg Thr Leu 585 590 595 tgt gta gcc ttc aaa gaa att gct cca gat gat tat gaa aga att aac 2359 Cys Val Ala Phe Lys Glu Ile Ala Pro Asp Asp Tyr Glu Arg Ile Asn 600 605 610 aga cag ctc ata gag gca aaa atg gcc tta caa gac aga gaa gaa aaa 2407 Arg Gln Leu Ile Glu Ala Lys Met Ala Leu Gln Asp Arg Glu Glu Lys 615 620 625 atg gaa aaa gtt ttc gat gat att gag aca aac atg aat tta att gga 2455 Met Glu Lys Val Phe Asp Asp Ile Glu Thr Asn Met Asn Leu Ile Gly 630 635 640 gcc act gca gtt gaa gac aag cta caa gat caa gct gca gag acc att 2503 Ala Thr Ala Val Glu Asp Lys Leu Gln Asp Gln Ala Ala Glu Thr Ile 645 650 655 660 gaa gct ctg cat gca gca ggc ctg aaa gtc tgg gtg ctc act ggg gac 2551 Glu Ala Leu His Ala Ala Gly Leu Lys Val Trp Val Leu Thr Gly Asp 665 670 675 aag atg gag aca gct aaa tcc aca tgc tat gcc tgc cgc ctt ttc cag 2599 Lys Met Glu Thr Ala Lys Ser Thr Cys Tyr Ala Cys Arg Leu Phe Gln 680 685 690 acc aac act gag ctc tta gaa cta acc aca aaa acc att gaa gaa agt 2647 Thr Asn Thr Glu Leu Leu Glu Leu Thr Thr Lys Thr Ile Glu Glu Ser 695 700 705 gaa agg aaa gaa gat cga tta cat gaa tta ttg ata gaa tat cgc aag 2695 Glu Arg Lys Glu Asp Arg Leu His Glu Leu Leu Ile Glu Tyr Arg Lys 710 715 720 aaa ttg ctg cat gag ttt cct aaa agt act aga agc ttt aaa aaa gca 2743 Lys Leu Leu His Glu Phe Pro Lys Ser Thr Arg Ser Phe Lys Lys Ala 725 730 735 740 tgg aca gaa cat cag gaa tat gga tta atc ata gat ggc tcc aca ttg 2791 Trp Thr Glu His Gln Glu Tyr Gly Leu Ile Ile Asp Gly Ser Thr Leu 745 750 755 tca ctc ata cta aat tct agt caa gac tct agt tca aac aat tac aaa 2839 Ser Leu Ile Leu Asn Ser Ser Gln Asp Ser Ser Ser Asn Asn Tyr Lys 760 765 770 agc att ttc cta caa ata tgt atg aag tgt act gca gtg ctc tgc tgt 2887 Ser Ile Phe Leu Gln Ile Cys Met Lys Cys Thr Ala Val Leu Cys Cys 775 780 785 cgg atg gca cca tta cag aaa gcc cag att gtc aga atg gtg aag aat 2935 Arg Met Ala Pro Leu Gln Lys Ala Gln Ile Val Arg Met Val Lys Asn 790 795 800 tta aaa ggc agc cca ata act ctg tcg ata ggt gat ggt gcc aat gat 2983 Leu Lys Gly Ser Pro Ile Thr Leu Ser Ile Gly Asp Gly Ala Asn Asp 805 810 815 820 gtt agt atg atc ttg gaa tcc cat gtg gga ata ggt att aaa ggc aaa 3031 Val Ser Met Ile Leu Glu Ser His Val Gly Ile Gly Ile Lys Gly Lys 825 830 835 gaa ggt cgc caa gca gct agg aat agc gat tat tct gtt cca aag ttt 3079 Glu Gly Arg Gln Ala Ala Arg Asn Ser Asp Tyr Ser Val Pro Lys Phe 840 845 850 aaa cac tta aag aaa ctg ctg ttg gct cat gga cat cta tat tat gtg 3127 Lys His Leu Lys Lys Leu Leu Leu Ala His Gly His Leu Tyr Tyr Val 855 860 865 aga ata gca cac ctt gta cag tac ttc ttc tat aag aac ctt tgt ttc 3175 Arg Ile Ala His Leu Val Gln Tyr Phe Phe Tyr Lys Asn Leu Cys Phe 870 875 880 att ttg cca cag ttt ttg tac cag ttc ttc tgt gga ttc tca caa cag 3223 Ile Leu Pro Gln Phe Leu Tyr Gln Phe Phe Cys Gly Phe Ser Gln Gln 885 890 895 900 cca ctg tat gat gct gct tac ctt aca atg tac aat atc tgc ttc aca 3271 Pro Leu Tyr Asp Ala Ala Tyr Leu Thr Met Tyr Asn Ile Cys Phe Thr 905 910 915 tcc ttg ccc atc ctg gcc tat agt cta ctg gaa cag cac atc aac att 3319 Ser Leu Pro Ile Leu Ala Tyr Ser Leu Leu Glu Gln His Ile Asn Ile 920 925 930 gac act ctg acc tca gat ccc cga ttg tat atg aaa att tct ggc aat 3367 Asp Thr Leu Thr Ser Asp Pro Arg Leu Tyr Met Lys Ile Ser Gly Asn 935 940 945 gcc atg cta cag ttg ggc ccc ttc tta tat tgg aca ttt ctg gct gcc 3415 Ala Met Leu Gln Leu Gly Pro Phe Leu Tyr Trp Thr Phe Leu Ala Ala 950 955 960 ttt gaa ggg aca gtg ttc ttc ttt ggg act tac ttt ctt ttt cag act 3463 Phe Glu Gly Thr Val Phe Phe Phe Gly Thr Tyr Phe Leu Phe Gln Thr 965 970 975 980 gca tcc cta gaa gaa aat gga aag gta tac gga aac tgg act ttt gga 3511 Ala Ser Leu Glu Glu Asn Gly Lys Val Tyr Gly Asn Trp Thr Phe Gly 985 990 995 acc att gtt ttt aca gtc tta gta ttc act gta acc ctg aag ctt gcc 3559 Thr Ile Val Phe Thr Val Leu Val Phe Thr Val Thr Leu Lys Leu Ala 1000 1005 1010 ttg gat acc cga ttc tgg acg tgg ata aat cac ttt gtg att tgg ggt 3607 Leu Asp Thr Arg Phe Trp Thr Trp Ile Asn His Phe Val Ile Trp Gly 1015 1020 1025 tct tta gcc ttc tat gta ttt ttc tca ttc ttc tgg gga gga att att 3655 Ser Leu Ala Phe Tyr Val Phe Phe Ser Phe Phe Trp Gly Gly Ile Ile 1030 1035 1040 tgg cct ttt ctc aag caa cag aga atg tat ttt gta ttt gcc caa atg 3703 Trp Pro Phe Leu Lys Gln Gln Arg Met Tyr Phe Val Phe Ala Gln Met 1045 1050 1055 1060 ctg tct tct gta tcc aca tgg ttg gct ata att ctt cta ata ttt atc 3751 Leu Ser Ser Val Ser Thr Trp Leu Ala Ile Ile Leu Leu Ile Phe Ile 1065 1070 1075 agc ctg ttc cct gag att ctt ctg ata gta tta aag aat gta aga aga 3799 Ser Leu Phe Pro Glu Ile Leu Leu Ile Val Leu Lys Asn Val Arg Arg 1080 1085 1090 aga agt gcc agg aga aat ctg agc tgt aga agg gca tct gac tca tta 3847 Arg Ser Ala Arg Arg Asn Leu Ser Cys Arg Arg Ala Ser Asp Ser Leu 1095 1100 1105 tcc gcc aga cct tca gtc aga cct ctt ctt tta cga aca ttc tca gac 3895 Ser Ala Arg Pro Ser Val Arg Pro Leu Leu Leu Arg Thr Phe Ser Asp 1110 1115 1120 gaa tct aat gta ttg taa cagaatccga atcttgaact gcctatgtta 3943 Glu Ser Asn Val Leu * 1125 ttgtcctaca agcatactga cagtggttac agctaaaaaa gaaagcatga agaaacaact 4003 acaaaaagtt atcatctcag gatacttgat atgcaacaca ctaaaccact ctcatgtcta 4063 gagttcacaa taaatgttca ttaaaatacc aaatgattct cttaagcatt taccattatt 4123 gtaagtagcc tttatggcca aagctgtaag ttaagaatta tatgaaagtt gaaagcaaga 4183 atacttagaa ttctggcttt agttagagta atataactca aatgggtgct cttttaaccc 4243 atgaactttg tgaatggatt taaatacaat agtatgaagt agaagttatg caatgagaat 4303 gaatagattt tgctaatact actttttttg cctggcagaa gaaatagact atttggatca 4363 catttctcat tcctcctaaa tgatcatctt aatttttttt cccaagtaca taaggaatac 4423 ttgaaaatac agaataacta aatagtatca atgcatcaga cagaatagtt aatcccttct 4483 gtttacccat gtgctactaa tgtcttggta gaatattctt gccaaaaaaa taccttgaac 4543 gcttatgtgg aaagtgttaa cttacgggta tttttgtggg aatagaaaaa aattgtttat 4603 tttttattct tctgaattaa accccactta tgggtgtaag cctactagac ttgaaaataa 4663 agtataaaac atttccaatc acttagtagc ccctcaaagt agttagaaaa taaacagatt 4723 tttccagtgt tgattttact gggatctgca gtaaggtggt ttaaaccata gttatataaa 4783 aataaaggtc attctgaata tcagcctttt ataattttat gtgaagagga agaaatatag 4843 cttattttaa acttttgacg gtttttattt gaaagagatt gcatttatgc atatatgcag 4903 tgctttttct taaacttggc caatttggaa agggggaagg agccacccca aaacggtggt 4963 tcagcttgta gagccatgac tctgtgaaga tgaatgttgt ctcttaactt ggacagggaa 5023 atggtctaac tctaaaccat gtaactgacc ttagtaaagt ccttgactaa ctgaactaga 5083 aggaaggttt agccttctaa ttagttcact tgaaacataa atgtgaaatg tcttcattca 5143 atgttaaaca catacttttt tggatataaa tgaccatatt tatttgactg ctagtttttt 5203 tgtttttttt ttgtctttct ggcatgcctg tactattatt aatgtttata ttgtaccttg 5263 atttggaaaa gtattggagt taatctgtat tatatttata tagtccatat ggcacatttg 5323 attcttccac atatattttg tgttaatgtt taggtatgat ttttttctaa attctagaaa 5383 agaacataat ttcagttatc agaagccatt ccatcattat agaccctttt tcattatttc 5443 atttgctctc atatatcagt attatttttg agcattttgt tacatgtcat tcacaactta 5503 cctaagtgtg ctgtgttctg gtagcccgta tttgaggtaa gctgctgaaa acaaaagtct 5563 ctatattctt tgcctattcc aaagagctaa aaaagtctaa cccaggaaag cttttgatat 5623 tttgtgtttg ttttcttgtt cttatggttg ttgttgctgt attatgattg ctgttttaca 5683 taaaatctat gggaactgtg aatacagaca agagagccac agtagagagg cttgtttaat 5743 gcagtaccat tggagagtta acagaataat ctagtagaaa aataactggt tgcatgtaaa 5803 attccttcca gccagaaaga aagaaagaca aggagtaagg gggatttaga gttatgtctc 5863 agctacacat tacattgtga tactgcagct caaattcaga atggcaatga tacatgatat 5923 catggcctag atccttgaga gggacctggc tttccttttt aaaagatatt ttactgaaga 5983 gctaaaaact ggccagtgtg gggttagcag atcgaataac ttgaaataga ccgtgcagta 6043 ttcctagcac tcaatgtaat caccctattt gtgacagaga aagggaaaaa aatataataa 6103 gatcatctac ctataatttg aataattttg agctatcaaa atgtctttgt aattttcaca 6163 accgctgtcc attgtttgag gatgttacct actaaactga aaacattcat tccatatcta 6223 cttacacata caccagcaac agtataaatg taagcctaac tttgcaaaat tcgtaataat 6283 ttagtgatgg aattttttaa taacatgcag tatataaatg tgcagatttt atgcgtgttg 6343 acaaaatcat ttttcagctt gcaaaatggg actgcaatat tacatttttc acttaagcag 6403 ttttttacat ctacgttgtt gctttctaaa atgaatgtga atgccatctt ttatgactgc 6463 aacttgcctt ttccattaca gaaatttttg tttgatgtaa tcaataaact ttggtatgat 6523 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 6582 <210> SEQ ID NO 14 <211> LENGTH: 1129 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 14 Met Phe Arg Arg Ser Leu Asn Arg Phe Cys Ala Gly Glu Glu Lys Arg 1 5 10 15 Val Gly Thr Arg Thr Val Phe Val Gly Asn His Pro Val Ser Glu Thr 20 25 30 Glu Ala Tyr Ile Ala Gln Arg Phe Cys Asp Asn Arg Ile Val Ser Ser 35 40 45 Lys Tyr Thr Leu Trp Asn Phe Leu Pro Lys Asn Leu Phe Glu Gln Phe 50 55 60 Arg Arg Ile Ala Asn Phe Tyr Phe Leu Ile Ile Phe Leu Val Gln Val 65 70 75 80 Thr Val Asp Thr Pro Thr Ser Pro Val Thr Ser Gly Leu Pro Leu Phe 85 90 95 Phe Val Ile Thr Val Thr Ala Ile Lys Gln Gly Tyr Glu Asp Trp Leu 100 105 110 Arg His Arg Ala Asp Asn Glu Val Asn Lys Ser Thr Val Tyr Ile Ile 115 120 125 Glu Asn Ala Lys Arg Val Arg Lys Glu Ser Glu Lys Ile Lys Val Gly 130 135 140 Asp Val Val Glu Val Gln Ala Asp Glu Thr Phe Pro Cys Asp Leu Ile 145 150 155 160 Leu Leu Ser Ser Cys Thr Thr Asp Gly Thr Cys Tyr Val Thr Thr Ala 165 170 175 Ser Leu Asp Gly Glu Ser Asn Cys Lys Thr His Tyr Ala Val Arg Asp 180 185 190 Thr Ile Ala Leu Cys Thr Ala Glu Ser Ile Asp Thr Leu Arg Ala Ala 195 200 205 Ile Glu Cys Glu Gln Pro Gln Pro Asp Leu Tyr Lys Phe Val Gly Arg 210 215 220 Ile Asn Ile Tyr Ser Asn Ser Leu Glu Ala Val Ala Arg Ser Leu Gly 225 230 235 240 Pro Glu Asn Leu Leu Leu Lys Gly Ala Thr Leu Lys Asn Thr Glu Lys 245 250 255 Ile Tyr Gly Val Ala Val Tyr Thr Gly Met Glu Thr Lys Met Ala Leu 260 265 270 Asn Tyr Gln Gly Lys Ser Gln Lys Arg Ser Ala Val Glu Lys Ser Ile 275 280 285 Asn Ala Phe Leu Ile Val Tyr Leu Phe Ile Leu Leu Thr Lys Ala Ala 290 295 300 Val Cys Thr Thr Leu Lys Tyr Val Trp Gln Ser Thr Pro Tyr Asn Asp 305 310 315 320 Glu Pro Trp Tyr Asn Gln Lys Thr Gln Lys Glu Arg Glu Thr Leu Lys 325 330 335 Val Leu Lys Met Phe Thr Asp Phe Leu Ser Phe Met Val Leu Phe Asn 340 345 350 Phe Ile Ile Pro Val Ser Met Tyr Val Thr Val Glu Met Gln Lys Phe 355 360 365 Leu Gly Ser Phe Phe Ile Ser Trp Asp Lys Asp Phe Tyr Asp Glu Glu 370 375 380 Ile Asn Glu Gly Ala Leu Val Asn Thr Ser Asp Leu Asn Glu Glu Leu 385 390 395 400 Gly Gln Val Asp Tyr Val Phe Thr Asp Lys Thr Gly Thr Leu Thr Glu 405 410 415 Asn Ser Met Glu Phe Ile Glu Cys Cys Ile Asp Gly His Lys Tyr Lys 420 425 430 Gly Val Thr Gln Glu Val Asp Gly Leu Ser Gln Thr Asp Gly Thr Leu 435 440 445 Thr Tyr Phe Asp Lys Val Asp Lys Asn Arg Glu Glu Leu Phe Leu Arg 450 455 460 Ala Leu Cys Leu Cys His Thr Val Glu Ile Lys Thr Asn Asp Ala Val 465 470 475 480 Asp Gly Ala Thr Glu Ser Ala Glu Leu Thr Tyr Ile Ser Ser Ser Pro 485 490 495 Asp Glu Ile Ala Leu Val Lys Gly Ala Lys Arg Tyr Gly Phe Thr Phe 500 505 510 Leu Gly Asn Arg Asn Gly Tyr Met Arg Val Glu Asn Gln Arg Lys Glu 515 520 525 Ile Glu Glu Tyr Glu Leu Leu His Thr Leu Asn Phe Asp Ala Val Arg 530 535 540 Arg Arg Met Ser Val Ile Val Lys Thr Gln Glu Gly Asp Ile Leu Leu 545 550 555 560 Phe Cys Lys Gly Ala Asp Ser Ala Val Phe Pro Arg Val Gln Asn His 565 570 575 Glu Ile Glu Leu Thr Lys Val His Val Glu Arg Asn Ala Met Asp Gly 580 585 590 Tyr Arg Thr Leu Cys Val Ala Phe Lys Glu Ile Ala Pro Asp Asp Tyr 595 600 605 Glu Arg Ile Asn Arg Gln Leu Ile Glu Ala Lys Met Ala Leu Gln Asp 610 615 620 Arg Glu Glu Lys Met Glu Lys Val Phe Asp Asp Ile Glu Thr Asn Met 625 630 635 640 Asn Leu Ile Gly Ala Thr Ala Val Glu Asp Lys Leu Gln Asp Gln Ala 645 650 655 Ala Glu Thr Ile Glu Ala Leu His Ala Ala Gly Leu Lys Val Trp Val 660 665 670 Leu Thr Gly Asp Lys Met Glu Thr Ala Lys Ser Thr Cys Tyr Ala Cys 675 680 685 Arg Leu Phe Gln Thr Asn Thr Glu Leu Leu Glu Leu Thr Thr Lys Thr 690 695 700 Ile Glu Glu Ser Glu Arg Lys Glu Asp Arg Leu His Glu Leu Leu Ile 705 710 715 720 Glu Tyr Arg Lys Lys Leu Leu His Glu Phe Pro Lys Ser Thr Arg Ser 725 730 735 Phe Lys Lys Ala Trp Thr Glu His Gln Glu Tyr Gly Leu Ile Ile Asp 740 745 750 Gly Ser Thr Leu Ser Leu Ile Leu Asn Ser Ser Gln Asp Ser Ser Ser 755 760 765 Asn Asn Tyr Lys Ser Ile Phe Leu Gln Ile Cys Met Lys Cys Thr Ala 770 775 780 Val Leu Cys Cys Arg Met Ala Pro Leu Gln Lys Ala Gln Ile Val Arg 785 790 795 800 Met Val Lys Asn Leu Lys Gly Ser Pro Ile Thr Leu Ser Ile Gly Asp 805 810 815 Gly Ala Asn Asp Val Ser Met Ile Leu Glu Ser His Val Gly Ile Gly 820 825 830 Ile Lys Gly Lys Glu Gly Arg Gln Ala Ala Arg Asn Ser Asp Tyr Ser 835 840 845 Val Pro Lys Phe Lys His Leu Lys Lys Leu Leu Leu Ala His Gly His 850 855 860 Leu Tyr Tyr Val Arg Ile Ala His Leu Val Gln Tyr Phe Phe Tyr Lys 865 870 875 880 Asn Leu Cys Phe Ile Leu Pro Gln Phe Leu Tyr Gln Phe Phe Cys Gly 885 890 895 Phe Ser Gln Gln Pro Leu Tyr Asp Ala Ala Tyr Leu Thr Met Tyr Asn 900 905 910 Ile Cys Phe Thr Ser Leu Pro Ile Leu Ala Tyr Ser Leu Leu Glu Gln 915 920 925 His Ile Asn Ile Asp Thr Leu Thr Ser Asp Pro Arg Leu Tyr Met Lys 930 935 940 Ile Ser Gly Asn Ala Met Leu Gln Leu Gly Pro Phe Leu Tyr Trp Thr 945 950 955 960 Phe Leu Ala Ala Phe Glu Gly Thr Val Phe Phe Phe Gly Thr Tyr Phe 965 970 975 Leu Phe Gln Thr Ala Ser Leu Glu Glu Asn Gly Lys Val Tyr Gly Asn 980 985 990 Trp Thr Phe Gly Thr Ile Val Phe Thr Val Leu Val Phe Thr Val Thr 995 1000 1005 Leu Lys Leu Ala Leu Asp Thr Arg Phe Trp Thr Trp Ile Asn His Phe 1010 1015 1020 Val Ile Trp Gly Ser Leu Ala Phe Tyr Val Phe Phe Ser Phe Phe Trp 1025 1030 1035 1040 Gly Gly Ile Ile Trp Pro Phe Leu Lys Gln Gln Arg Met Tyr Phe Val 1045 1050 1055 Phe Ala Gln Met Leu Ser Ser Val Ser Thr Trp Leu Ala Ile Ile Leu 1060 1065 1070 Leu Ile Phe Ile Ser Leu Phe Pro Glu Ile Leu Leu Ile Val Leu Lys 1075 1080 1085 Asn Val Arg Arg Arg Ser Ala Arg Arg Asn Leu Ser Cys Arg Arg Ala 1090 1095 1100 Ser Asp Ser Leu Ser Ala Arg Pro Ser Val Arg Pro Leu Leu Leu Arg 1105 1110 1115 1120 Thr Phe Ser Asp Glu Ser Asn Val Leu 1125 <210> SEQ ID NO 15 <211> LENGTH: 3390 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(3390) <400> SEQUENCE: 15 atg ttc cgc cgg agc ttg aat cgt ttt tgt gct gga gaa gag aaa cga 48 Met Phe Arg Arg Ser Leu Asn Arg Phe Cys Ala Gly Glu Glu Lys Arg 1 5 10 15 gtt ggc aca cgc aca gtg ttt gtt ggc aat cat cca gtt tcg gaa aca 96 Val Gly Thr Arg Thr Val Phe Val Gly Asn His Pro Val Ser Glu Thr 20 25 30 gaa gct tac att gca caa aga ttt tgt gat aat aga ata gtc tca tct 144 Glu Ala Tyr Ile Ala Gln Arg Phe Cys Asp Asn Arg Ile Val Ser Ser 35 40 45 aag tat aca ctt tgg aat ttt ctc cca aag aat ctg ttt gaa cag ttt 192 Lys Tyr Thr Leu Trp Asn Phe Leu Pro Lys Asn Leu Phe Glu Gln Phe 50 55 60 aga aga att gca aat ttt tat ttt ctc ata atc ttc ctt gta cag gtc 240 Arg Arg Ile Ala Asn Phe Tyr Phe Leu Ile Ile Phe Leu Val Gln Val 65 70 75 80 aca gta gac aca cca act agc cca gtt acc agt gga ctt cca ctt ttc 288 Thr Val Asp Thr Pro Thr Ser Pro Val Thr Ser Gly Leu Pro Leu Phe 85 90 95 ttt gtt ata act gtt aca gcc atc aag cag gga tat gag gat tgg ctg 336 Phe Val Ile Thr Val Thr Ala Ile Lys Gln Gly Tyr Glu Asp Trp Leu 100 105 110 aga cac aga gct gac aat gaa gtc aac aaa agc act gtt tac att att 384 Arg His Arg Ala Asp Asn Glu Val Asn Lys Ser Thr Val Tyr Ile Ile 115 120 125 gaa aat gca aag cga gtg aga aaa gaa agt gaa aaa atc aag gtt ggt 432 Glu Asn Ala Lys Arg Val Arg Lys Glu Ser Glu Lys Ile Lys Val Gly 130 135 140 gat gta gta gaa gta cag gca gat gaa acc ttt ccc tgt gat ctt att 480 Asp Val Val Glu Val Gln Ala Asp Glu Thr Phe Pro Cys Asp Leu Ile 145 150 155 160 ctt cta tca tct tgc acc act gat gga acc tgt tat gtc act aca gcc 528 Leu Leu Ser Ser Cys Thr Thr Asp Gly Thr Cys Tyr Val Thr Thr Ala 165 170 175 agt ctt gat ggg gaa tcc aat tgc aag aca cat tat gca gta cgt gat 576 Ser Leu Asp Gly Glu Ser Asn Cys Lys Thr His Tyr Ala Val Arg Asp 180 185 190 acc att gca ctg tgt aca gca gaa tcc atc gat acc ctc cga gca gca 624 Thr Ile Ala Leu Cys Thr Ala Glu Ser Ile Asp Thr Leu Arg Ala Ala 195 200 205 att gaa tgt gaa cag cct caa cct gac ctc tac aaa ttt gtt ggg cga 672 Ile Glu Cys Glu Gln Pro Gln Pro Asp Leu Tyr Lys Phe Val Gly Arg 210 215 220 atc aat atc tac agt aat agt ctt gag gct gtt gcc agg tct ttg gga 720 Ile Asn Ile Tyr Ser Asn Ser Leu Glu Ala Val Ala Arg Ser Leu Gly 225 230 235 240 cct gaa aat ctc ttg ctg aaa gga gct acg cta aaa aat acc gag aag 768 Pro Glu Asn Leu Leu Leu Lys Gly Ala Thr Leu Lys Asn Thr Glu Lys 245 250 255 ata tat gga gtt gct gtt tac act gga atg gaa acc aaa atg gct ttg 816 Ile Tyr Gly Val Ala Val Tyr Thr Gly Met Glu Thr Lys Met Ala Leu 260 265 270 aac tac caa ggg aaa tct cag aaa cgt tct gct gtt gaa aaa tct att 864 Asn Tyr Gln Gly Lys Ser Gln Lys Arg Ser Ala Val Glu Lys Ser Ile 275 280 285 aat gct ttc ctg att gta tat tta ttt atc tta ctg acc aaa gct gca 912 Asn Ala Phe Leu Ile Val Tyr Leu Phe Ile Leu Leu Thr Lys Ala Ala 290 295 300 gta tgc act act cta aag tat gtt tgg caa agt acc cca tac aat gat 960 Val Cys Thr Thr Leu Lys Tyr Val Trp Gln Ser Thr Pro Tyr Asn Asp 305 310 315 320 gaa cct tgg tat aac caa aag act cag aaa gag cga gag acc ttg aag 1008 Glu Pro Trp Tyr Asn Gln Lys Thr Gln Lys Glu Arg Glu Thr Leu Lys 325 330 335 gtt tta aaa atg ttc acc gac ttc cta tca ttt atg gtt cta ttc aac 1056 Val Leu Lys Met Phe Thr Asp Phe Leu Ser Phe Met Val Leu Phe Asn 340 345 350 ttt atc att cct gtc tcc atg tac gtc aca gta gaa atg cag aaa ttc 1104 Phe Ile Ile Pro Val Ser Met Tyr Val Thr Val Glu Met Gln Lys Phe 355 360 365 ttg ggc tcc ttc ttc atc tca tgg gat aag gac ttt tat gat gaa gaa 1152 Leu Gly Ser Phe Phe Ile Ser Trp Asp Lys Asp Phe Tyr Asp Glu Glu 370 375 380 att aat gaa gga gcc ctg gtt aac aca tca gac ctt aat gaa gaa ctt 1200 Ile Asn Glu Gly Ala Leu Val Asn Thr Ser Asp Leu Asn Glu Glu Leu 385 390 395 400 ggt cag gtg gat tat gta ttt aca gat aag act gga aca ctc act gaa 1248 Gly Gln Val Asp Tyr Val Phe Thr Asp Lys Thr Gly Thr Leu Thr Glu 405 410 415 aac agc atg gaa ttc att gaa tgc tgc ata gat ggc cac aaa tat aaa 1296 Asn Ser Met Glu Phe Ile Glu Cys Cys Ile Asp Gly His Lys Tyr Lys 420 425 430 ggt gta act caa gag gtt gat gga tta tct caa act gat gga act tta 1344 Gly Val Thr Gln Glu Val Asp Gly Leu Ser Gln Thr Asp Gly Thr Leu 435 440 445 aca tat ttt gac aaa gta gat aag aat cga gaa gag ctg ttt cta cgt 1392 Thr Tyr Phe Asp Lys Val Asp Lys Asn Arg Glu Glu Leu Phe Leu Arg 450 455 460 gcc ttg tgt tta tgt cat act gta gaa atc aaa aca aac gat gct gtt 1440 Ala Leu Cys Leu Cys His Thr Val Glu Ile Lys Thr Asn Asp Ala Val 465 470 475 480 gat gga gct aca gaa tca gct gaa tta acc tat atc tcc tct tca cca 1488 Asp Gly Ala Thr Glu Ser Ala Glu Leu Thr Tyr Ile Ser Ser Ser Pro 485 490 495 gat gaa ata gct ttg gtg aaa gga gct aaa agg tac ggg ttc aca ttt 1536 Asp Glu Ile Ala Leu Val Lys Gly Ala Lys Arg Tyr Gly Phe Thr Phe 500 505 510 tta gga aat cga aat gga tat atg aga gta gag aac caa aga aaa gaa 1584 Leu Gly Asn Arg Asn Gly Tyr Met Arg Val Glu Asn Gln Arg Lys Glu 515 520 525 ata gaa gaa tat gaa ctt ctt cac acc tta aac ttt gat gct gtc cgg 1632 Ile Glu Glu Tyr Glu Leu Leu His Thr Leu Asn Phe Asp Ala Val Arg 530 535 540 cga cgt atg agt gta att gtg aag act caa gaa gga gac ata ctt ctc 1680 Arg Arg Met Ser Val Ile Val Lys Thr Gln Glu Gly Asp Ile Leu Leu 545 550 555 560 ttt tgt aaa gga gca gac tcg gca gtt ttt ccc aga gtg caa aat cat 1728 Phe Cys Lys Gly Ala Asp Ser Ala Val Phe Pro Arg Val Gln Asn His 565 570 575 gaa att gag tta act aaa gtc cat gtg gaa cgt aat gca atg gat ggg 1776 Glu Ile Glu Leu Thr Lys Val His Val Glu Arg Asn Ala Met Asp Gly 580 585 590 tat cgg aca ctc tgt gta gcc ttc aaa gaa att gct cca gat gat tat 1824 Tyr Arg Thr Leu Cys Val Ala Phe Lys Glu Ile Ala Pro Asp Asp Tyr 595 600 605 gaa aga att aac aga cag ctc ata gag gca aaa atg gcc tta caa gac 1872 Glu Arg Ile Asn Arg Gln Leu Ile Glu Ala Lys Met Ala Leu Gln Asp 610 615 620 aga gaa gaa aaa atg gaa aaa gtt ttc gat gat att gag aca aac atg 1920 Arg Glu Glu Lys Met Glu Lys Val Phe Asp Asp Ile Glu Thr Asn Met 625 630 635 640 aat tta att gga gcc act gca gtt gaa gac aag cta caa gat caa gct 1968 Asn Leu Ile Gly Ala Thr Ala Val Glu Asp Lys Leu Gln Asp Gln Ala 645 650 655 gca gag acc att gaa gct ctg cat gca gca ggc ctg aaa gtc tgg gtg 2016 Ala Glu Thr Ile Glu Ala Leu His Ala Ala Gly Leu Lys Val Trp Val 660 665 670 ctc act ggg gac aag atg gag aca gct aaa tcc aca tgc tat gcc tgc 2064 Leu Thr Gly Asp Lys Met Glu Thr Ala Lys Ser Thr Cys Tyr Ala Cys 675 680 685 cgc ctt ttc cag acc aac act gag ctc tta gaa cta acc aca aaa acc 2112 Arg Leu Phe Gln Thr Asn Thr Glu Leu Leu Glu Leu Thr Thr Lys Thr 690 695 700 att gaa gaa agt gaa agg aaa gaa gat cga tta cat gaa tta ttg ata 2160 Ile Glu Glu Ser Glu Arg Lys Glu Asp Arg Leu His Glu Leu Leu Ile 705 710 715 720 gaa tat cgc aag aaa ttg ctg cat gag ttt cct aaa agt act aga agc 2208 Glu Tyr Arg Lys Lys Leu Leu His Glu Phe Pro Lys Ser Thr Arg Ser 725 730 735 ttt aaa aaa gca tgg aca gaa cat cag gaa tat gga tta atc ata gat 2256 Phe Lys Lys Ala Trp Thr Glu His Gln Glu Tyr Gly Leu Ile Ile Asp 740 745 750 ggc tcc aca ttg tca ctc ata cta aat tct agt caa gac tct agt tca 2304 Gly Ser Thr Leu Ser Leu Ile Leu Asn Ser Ser Gln Asp Ser Ser Ser 755 760 765 aac aat tac aaa agc att ttc cta caa ata tgt atg aag tgt act gca 2352 Asn Asn Tyr Lys Ser Ile Phe Leu Gln Ile Cys Met Lys Cys Thr Ala 770 775 780 gtg ctc tgc tgt cgg atg gca cca tta cag aaa gcc cag att gtc aga 2400 Val Leu Cys Cys Arg Met Ala Pro Leu Gln Lys Ala Gln Ile Val Arg 785 790 795 800 atg gtg aag aat tta aaa ggc agc cca ata act ctg tcg ata ggt gat 2448 Met Val Lys Asn Leu Lys Gly Ser Pro Ile Thr Leu Ser Ile Gly Asp 805 810 815 ggt gcc aat gat gtt agt atg atc ttg gaa tcc cat gtg gga ata ggt 2496 Gly Ala Asn Asp Val Ser Met Ile Leu Glu Ser His Val Gly Ile Gly 820 825 830 att aaa ggc aaa gaa ggt cgc caa gca gct agg aat agc gat tat tct 2544 Ile Lys Gly Lys Glu Gly Arg Gln Ala Ala Arg Asn Ser Asp Tyr Ser 835 840 845 gtt cca aag ttt aaa cac tta aag aaa ctg ctg ttg gct cat gga cat 2592 Val Pro Lys Phe Lys His Leu Lys Lys Leu Leu Leu Ala His Gly His 850 855 860 cta tat tat gtg aga ata gca cac ctt gta cag tac ttc ttc tat aag 2640 Leu Tyr Tyr Val Arg Ile Ala His Leu Val Gln Tyr Phe Phe Tyr Lys 865 870 875 880 aac ctt tgt ttc att ttg cca cag ttt ttg tac cag ttc ttc tgt gga 2688 Asn Leu Cys Phe Ile Leu Pro Gln Phe Leu Tyr Gln Phe Phe Cys Gly 885 890 895 ttc tca caa cag cca ctg tat gat gct gct tac ctt aca atg tac aat 2736 Phe Ser Gln Gln Pro Leu Tyr Asp Ala Ala Tyr Leu Thr Met Tyr Asn 900 905 910 atc tgc ttc aca tcc ttg ccc atc ctg gcc tat agt cta ctg gaa cag 2784 Ile Cys Phe Thr Ser Leu Pro Ile Leu Ala Tyr Ser Leu Leu Glu Gln 915 920 925 cac atc aac att gac act ctg acc tca gat ccc cga ttg tat atg aaa 2832 His Ile Asn Ile Asp Thr Leu Thr Ser Asp Pro Arg Leu Tyr Met Lys 930 935 940 att tct ggc aat gcc atg cta cag ttg ggc ccc ttc tta tat tgg aca 2880 Ile Ser Gly Asn Ala Met Leu Gln Leu Gly Pro Phe Leu Tyr Trp Thr 945 950 955 960 ttt ctg gct gcc ttt gaa ggg aca gtg ttc ttc ttt ggg act tac ttt 2928 Phe Leu Ala Ala Phe Glu Gly Thr Val Phe Phe Phe Gly Thr Tyr Phe 965 970 975 ctt ttt cag act gca tcc cta gaa gaa aat gga aag gta tac gga aac 2976 Leu Phe Gln Thr Ala Ser Leu Glu Glu Asn Gly Lys Val Tyr Gly Asn 980 985 990 tgg act ttt gga acc att gtt ttt aca gtc tta gta ttc act gta acc 3024 Trp Thr Phe Gly Thr Ile Val Phe Thr Val Leu Val Phe Thr Val Thr 995 1000 1005 ctg aag ctt gcc ttg gat acc cga ttc tgg acg tgg ata aat cac ttt 3072 Leu Lys Leu Ala Leu Asp Thr Arg Phe Trp Thr Trp Ile Asn His Phe 1010 1015 1020 gtg att tgg ggt tct tta gcc ttc tat gta ttt ttc tca ttc ttc tgg 3120 Val Ile Trp Gly Ser Leu Ala Phe Tyr Val Phe Phe Ser Phe Phe Trp 1025 1030 1035 1040 gga gga att att tgg cct ttt ctc aag caa cag aga atg tat ttt gta 3168 Gly Gly Ile Ile Trp Pro Phe Leu Lys Gln Gln Arg Met Tyr Phe Val 1045 1050 1055 ttt gcc caa atg ctg tct tct gta tcc aca tgg ttg gct ata att ctt 3216 Phe Ala Gln Met Leu Ser Ser Val Ser Thr Trp Leu Ala Ile Ile Leu 1060 1065 1070 cta ata ttt atc agc ctg ttc cct gag att ctt ctg ata gta tta aag 3264 Leu Ile Phe Ile Ser Leu Phe Pro Glu Ile Leu Leu Ile Val Leu Lys 1075 1080 1085 aat gta aga aga aga agt gcc agg aga aat ctg agc tgt aga agg gca 3312 Asn Val Arg Arg Arg Ser Ala Arg Arg Asn Leu Ser Cys Arg Arg Ala 1090 1095 1100 tct gac tca tta tcc gcc aga cct tca gtc aga cct ctt ctt tta cga 3360 Ser Asp Ser Leu Ser Ala Arg Pro Ser Val Arg Pro Leu Leu Leu Arg 1105 1110 1115 1120 aca ttc tca gac gaa tct aat gta ttg taa 3390 Thr Phe Ser Asp Glu Ser Asn Val Leu * 1125 <210> SEQ ID NO 16 <211> LENGTH: 6073 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (273)...(4553) <400> SEQUENCE: 16 ccacgcgtcc gggaggagcg gagggagaag taggttgcga gctcagcaca ggctccggcg 60 ctggctcccg cagctgagtt tgggagatgt ctaagtgatt tttttttttc ccggaaggca 120 aatggctggc gtggaagcac aacccgcttt cactcttcga atttgtgctt agctcttttc 180 ttgtaccttg cgactcgtga ccaacatgct gtgatgtgtg ccgagggagg aattggtcag 240 ctacacaacc tggatcttac cacagtttgg at atg act gag gct ctc caa tgg 293 Met Thr Glu Ala Leu Gln Trp 1 5 gcc aga tat cac tgg cga cgg ctg atc aga ggt gca acc agg gat gat 341 Ala Arg Tyr His Trp Arg Arg Leu Ile Arg Gly Ala Thr Arg Asp Asp 10 15 20 gat tca ggg cca tac aac tat tcc tcg ttg ctc gcc tgt ggg cgc aag 389 Asp Ser Gly Pro Tyr Asn Tyr Ser Ser Leu Leu Ala Cys Gly Arg Lys 25 30 35 tcc tct cag atc cct aaa ctg tca gga agg cac cgg att gtt gtt ccc 437 Ser Ser Gln Ile Pro Lys Leu Ser Gly Arg His Arg Ile Val Val Pro 40 45 50 55 cac atc cag ccc ttc aag gat gag tat gag aag ttc tcc gga gcc tat 485 His Ile Gln Pro Phe Lys Asp Glu Tyr Glu Lys Phe Ser Gly Ala Tyr 60 65 70 gtg aac aat cga ata cga aca aca aag tac aca ctt ctg aat ttt gtg 533 Val Asn Asn Arg Ile Arg Thr Thr Lys Tyr Thr Leu Leu Asn Phe Val 75 80 85 cca aga aat tta ttt gaa caa ttt cac aga gct gcc agt tta tat ttc 581 Pro Arg Asn Leu Phe Glu Gln Phe His Arg Ala Ala Ser Leu Tyr Phe 90 95 100 ctg ttc cta gtt gtc ctg aac tgg gta cct ttg gta gaa gcc ttc caa 629 Leu Phe Leu Val Val Leu Asn Trp Val Pro Leu Val Glu Ala Phe Gln 105 110 115 aag gaa atc acc atg ttg cct ctg gtg gtg gtc ctt aca att atc gca 677 Lys Glu Ile Thr Met Leu Pro Leu Val Val Val Leu Thr Ile Ile Ala 120 125 130 135 att aaa gat ggc ctg gaa gat tat cgg aaa tac aaa att gac aaa cag 725 Ile Lys Asp Gly Leu Glu Asp Tyr Arg Lys Tyr Lys Ile Asp Lys Gln 140 145 150 atc aat aat tta ata act aaa gtt tat agt agg aaa gag aaa aaa tac 773 Ile Asn Asn Leu Ile Thr Lys Val Tyr Ser Arg Lys Glu Lys Lys Tyr 155 160 165 att gac cga tgc tgg aaa gac gtt act gtt ggg gac ttt att cgc ctc 821 Ile Asp Arg Cys Trp Lys Asp Val Thr Val Gly Asp Phe Ile Arg Leu 170 175 180 tcc tgc aat gag gtc atc cct gca gac atg gta cta ctc ttt tcc act 869 Ser Cys Asn Glu Val Ile Pro Ala Asp Met Val Leu Leu Phe Ser Thr 185 190 195 gat cca gat gga atc tgt cac att gag act tct ggt ctt gat gga gag 917 Asp Pro Asp Gly Ile Cys His Ile Glu Thr Ser Gly Leu Asp Gly Glu 200 205 210 215 agc aat tta aaa cag agg cag gtg gtt cgg gga tat gca gaa cag gac 965 Ser Asn Leu Lys Gln Arg Gln Val Val Arg Gly Tyr Ala Glu Gln Asp 220 225 230 tct gaa gtt gat cct gag aag ttt tcc agt agg ata gaa tgt gaa agc 1013 Ser Glu Val Asp Pro Glu Lys Phe Ser Ser Arg Ile Glu Cys Glu Ser 235 240 245 cca aac aat gac ctc agc aga ttc cga ggc ttc cta gaa cat tcc aac 1061 Pro Asn Asn Asp Leu Ser Arg Phe Arg Gly Phe Leu Glu His Ser Asn 250 255 260 aaa gaa cgc gtg ggt ctc agt aaa gaa aat ttg ttg ctt aga gga tgc 1109 Lys Glu Arg Val Gly Leu Ser Lys Glu Asn Leu Leu Leu Arg Gly Cys 265 270 275 acc att aga aac aca gag gct gtt gtg ggc att gtg gtt tat gca ggc 1157 Thr Ile Arg Asn Thr Glu Ala Val Val Gly Ile Val Val Tyr Ala Gly 280 285 290 295 cat gaa acc aaa gca atg ctg aac aac agt ggg cca cgg tat aag cgc 1205 His Glu Thr Lys Ala Met Leu Asn Asn Ser Gly Pro Arg Tyr Lys Arg 300 305 310 agc aaa tta gaa aga aga gca aac aca gat gtc ctc tgg tgt gtc atg 1253 Ser Lys Leu Glu Arg Arg Ala Asn Thr Asp Val Leu Trp Cys Val Met 315 320 325 ctt ctg gtc ata atg tgc tta act ggc gca gta ggt cat gga atc tgg 1301 Leu Leu Val Ile Met Cys Leu Thr Gly Ala Val Gly His Gly Ile Trp 330 335 340 ctg agc agg tat gaa aag atg cat ttt ttc aat gtt ccc gag cct gat 1349 Leu Ser Arg Tyr Glu Lys Met His Phe Phe Asn Val Pro Glu Pro Asp 345 350 355 gga cat atc ata tca cca ctg ttg gca gga ttt tat atg ttt tgg acc 1397 Gly His Ile Ile Ser Pro Leu Leu Ala Gly Phe Tyr Met Phe Trp Thr 360 365 370 375 atg atc att ttg tta cag gtc ttg att cct att tct ctc tat gtt tcc 1445 Met Ile Ile Leu Leu Gln Val Leu Ile Pro Ile Ser Leu Tyr Val Ser 380 385 390 atc gaa att gtg aag ctt gga caa ata tat ttc att caa agt gat gtg 1493 Ile Glu Ile Val Lys Leu Gly Gln Ile Tyr Phe Ile Gln Ser Asp Val 395 400 405 gat ttc tac aat gaa aaa atg gat tct att gtt cag tgc cga gcc ctg 1541 Asp Phe Tyr Asn Glu Lys Met Asp Ser Ile Val Gln Cys Arg Ala Leu 410 415 420 aac atc gcc gag gat ctg gga cag att cag tac ctc ttt tcc gat aag 1589 Asn Ile Ala Glu Asp Leu Gly Gln Ile Gln Tyr Leu Phe Ser Asp Lys 425 430 435 aca gga acc ctc act gag aat aag atg gtt ttt cga aga tgt agt gtg 1637 Thr Gly Thr Leu Thr Glu Asn Lys Met Val Phe Arg Arg Cys Ser Val 440 445 450 455 gca gga ttt gat tac tgc cat gaa gaa aat gcc agg agg ttg gag tcc 1685 Ala Gly Phe Asp Tyr Cys His Glu Glu Asn Ala Arg Arg Leu Glu Ser 460 465 470 tat cag gaa gct gtc tct gaa gat gaa gat ttt ata gac aca gtc agt 1733 Tyr Gln Glu Ala Val Ser Glu Asp Glu Asp Phe Ile Asp Thr Val Ser 475 480 485 ggt tcc ctc agc aat atg gca aaa ccg aga gcc ccc agc tgc agg aca 1781 Gly Ser Leu Ser Asn Met Ala Lys Pro Arg Ala Pro Ser Cys Arg Thr 490 495 500 gtt cat aat ggg cct ttg gga aat aag ccc tca aat cat ctt gct ggg 1829 Val His Asn Gly Pro Leu Gly Asn Lys Pro Ser Asn His Leu Ala Gly 505 510 515 agc tct ttt act cta gga agt gga gaa gga gcc agt gaa gtg cct cat 1877 Ser Ser Phe Thr Leu Gly Ser Gly Glu Gly Ala Ser Glu Val Pro His 520 525 530 535 tcc aga cag gct gct ttc agt agc ccc att gaa aca gac gtg gta cca 1925 Ser Arg Gln Ala Ala Phe Ser Ser Pro Ile Glu Thr Asp Val Val Pro 540 545 550 gac acc agg ctt tta gac aaa ttt agt cag att aca cct cgg ctc ttt 1973 Asp Thr Arg Leu Leu Asp Lys Phe Ser Gln Ile Thr Pro Arg Leu Phe 555 560 565 atg cca cta gat gag acc atc caa aat cca cca atg gaa act ttg tac 2021 Met Pro Leu Asp Glu Thr Ile Gln Asn Pro Pro Met Glu Thr Leu Tyr 570 575 580 att atc gac ttt ttc att gca ttg gca att tgc aac aca gta gtg gtt 2069 Ile Ile Asp Phe Phe Ile Ala Leu Ala Ile Cys Asn Thr Val Val Val 585 590 595 tct gct cct aac caa ccc cga caa aag atc aga cac cct tca ctg ggg 2117 Ser Ala Pro Asn Gln Pro Arg Gln Lys Ile Arg His Pro Ser Leu Gly 600 605 610 615 ggg ttg ccc att aag tct ttg gaa gag att aaa agt ctt ttc cag aga 2165 Gly Leu Pro Ile Lys Ser Leu Glu Glu Ile Lys Ser Leu Phe Gln Arg 620 625 630 tgg tct gtc cga aga tca agt tct cca tcg ctt aac agt ggg aaa gag 2213 Trp Ser Val Arg Arg Ser Ser Ser Pro Ser Leu Asn Ser Gly Lys Glu 635 640 645 cca tct tct gga gtt cca aac gcc ttt gtg agc aga ctc cct ctc ttt 2261 Pro Ser Ser Gly Val Pro Asn Ala Phe Val Ser Arg Leu Pro Leu Phe 650 655 660 agt cga atg aaa cca gct tca cct gtg gag gaa gag gtc tcc cag gtg 2309 Ser Arg Met Lys Pro Ala Ser Pro Val Glu Glu Glu Val Ser Gln Val 665 670 675 tgt gag agc ccc cag tgc tcc agt agc tca gct tgc tgc aca gaa aca 2357 Cys Glu Ser Pro Gln Cys Ser Ser Ser Ser Ala Cys Cys Thr Glu Thr 680 685 690 695 gag aaa caa cac ggt gat gca ggc ctc ctg aat ggc aag gca gag tcc 2405 Glu Lys Gln His Gly Asp Ala Gly Leu Leu Asn Gly Lys Ala Glu Ser 700 705 710 ctc cct gga cag cca ttg gcc tgc aac ctg tgt tat gag gcc gag agc 2453 Leu Pro Gly Gln Pro Leu Ala Cys Asn Leu Cys Tyr Glu Ala Glu Ser 715 720 725 cca gac gaa gcg gcc tta gtg tat gcc gcc agg gct tac caa tgc act 2501 Pro Asp Glu Ala Ala Leu Val Tyr Ala Ala Arg Ala Tyr Gln Cys Thr 730 735 740 tta cgg tct cgg aca cca gag cag gtc atg gtg gac ttt gct gct ttg 2549 Leu Arg Ser Arg Thr Pro Glu Gln Val Met Val Asp Phe Ala Ala Leu 745 750 755 gga cca tta aca ttt caa ctc cta cac atc ctg ccc ttt gac tca gta 2597 Gly Pro Leu Thr Phe Gln Leu Leu His Ile Leu Pro Phe Asp Ser Val 760 765 770 775 aga aaa aga atg tct gtt gtg gtc cga cac cct ctt tcc aat caa gtt 2645 Arg Lys Arg Met Ser Val Val Val Arg His Pro Leu Ser Asn Gln Val 780 785 790 gtg gtg tat acg aaa ggc gct gat tct gtg atc atg gag tta ctg tcg 2693 Val Val Tyr Thr Lys Gly Ala Asp Ser Val Ile Met Glu Leu Leu Ser 795 800 805 gtg gct tcc cca gat gga gca agt ctg gag aaa caa cag atg ata gta 2741 Val Ala Ser Pro Asp Gly Ala Ser Leu Glu Lys Gln Gln Met Ile Val 810 815 820 agg gag aaa acc cag aag cac ttg gat gac tat gcc aaa caa ggc ctt 2789 Arg Glu Lys Thr Gln Lys His Leu Asp Asp Tyr Ala Lys Gln Gly Leu 825 830 835 cgt act tta tgt ata gca aag aag gtc atg agt gac act gaa tat gca 2837 Arg Thr Leu Cys Ile Ala Lys Lys Val Met Ser Asp Thr Glu Tyr Ala 840 845 850 855 gag tgg ctg agg aat cat ttt tta gct gaa acc agc att gac aac agg 2885 Glu Trp Leu Arg Asn His Phe Leu Ala Glu Thr Ser Ile Asp Asn Arg 860 865 870 gaa gaa tta cta ctt gaa tct gcc atg agg ttg gag aac aaa ctt aca 2933 Glu Glu Leu Leu Leu Glu Ser Ala Met Arg Leu Glu Asn Lys Leu Thr 875 880 885 tta ctt ggt gct act ggc att gaa gac cgt ctg cag gag gga gtc cct 2981 Leu Leu Gly Ala Thr Gly Ile Glu Asp Arg Leu Gln Glu Gly Val Pro 890 895 900 gaa tct ata gaa gct ctt cac aaa gcg ggc atc aag atc tgg atg ctg 3029 Glu Ser Ile Glu Ala Leu His Lys Ala Gly Ile Lys Ile Trp Met Leu 905 910 915 aca ggg gac aag cag gag aca gct gtc aac ata gct tat gca tgc aaa 3077 Thr Gly Asp Lys Gln Glu Thr Ala Val Asn Ile Ala Tyr Ala Cys Lys 920 925 930 935 cta ctg gag cca gat gac aag ctt ttt atc ctc aat acc caa agt aaa 3125 Leu Leu Glu Pro Asp Asp Lys Leu Phe Ile Leu Asn Thr Gln Ser Lys 940 945 950 gat gcc tgt ggg atg ctg atg agc aca att ttg aaa gaa ctt cag aag 3173 Asp Ala Cys Gly Met Leu Met Ser Thr Ile Leu Lys Glu Leu Gln Lys 955 960 965 aaa act caa gcc ctg cca gag caa gtg tca tta agt gaa gat tta ctt 3221 Lys Thr Gln Ala Leu Pro Glu Gln Val Ser Leu Ser Glu Asp Leu Leu 970 975 980 cag cct cct gtc ccc cgg gac tca ggg tta cga gct gga ctc att atc 3269 Gln Pro Pro Val Pro Arg Asp Ser Gly Leu Arg Ala Gly Leu Ile Ile 985 990 995 act ggg aag acc ctg gag ttt gcc ctg caa gaa agt ctg caa aag cag 3317 Thr Gly Lys Thr Leu Glu Phe Ala Leu Gln Glu Ser Leu Gln Lys Gln 1000 1005 1010 1015 ttc ctg gaa ctg aca tct tgg tgt caa gct gtg gtc tgc tgc cga gcc 3365 Phe Leu Glu Leu Thr Ser Trp Cys Gln Ala Val Val Cys Cys Arg Ala 1020 1025 1030 aca ccg ctg cag aaa agt gaa gtg gtg aaa ttg gtc cgc agc cat ctc 3413 Thr Pro Leu Gln Lys Ser Glu Val Val Lys Leu Val Arg Ser His Leu 1035 1040 1045 cag gtg atg acc ctt gct att ggt gat ggt gcc aat gat gtt agc atg 3461 Gln Val Met Thr Leu Ala Ile Gly Asp Gly Ala Asn Asp Val Ser Met 1050 1055 1060 ata caa gtg gca gac att ggg ata ggg gtc tca ggt caa gaa ggc atg 3509 Ile Gln Val Ala Asp Ile Gly Ile Gly Val Ser Gly Gln Glu Gly Met 1065 1070 1075 cag gct gtg atg gcc agt gac ttt gcc gtt tct cag ttc aaa cat ctc 3557 Gln Ala Val Met Ala Ser Asp Phe Ala Val Ser Gln Phe Lys His Leu 1080 1085 1090 1095 agc aag ctc ctt ctt gtc cat gga cac tgg tgt tat aca cgg ctt tcc 3605 Ser Lys Leu Leu Leu Val His Gly His Trp Cys Tyr Thr Arg Leu Ser 1100 1105 1110 aac atg att ctc tat ttt ttc tat aag aat gtg gcc tat gtg aac ctc 3653 Asn Met Ile Leu Tyr Phe Phe Tyr Lys Asn Val Ala Tyr Val Asn Leu 1115 1120 1125 ctt ttc tgg tac cag ttc ttt tgt gga ttt tca gga aca tcc atg act 3701 Leu Phe Trp Tyr Gln Phe Phe Cys Gly Phe Ser Gly Thr Ser Met Thr 1130 1135 1140 gat tac tgg gtt ttg atc ttc ttc aac ctc ctc ttc aca tct gcc cct 3749 Asp Tyr Trp Val Leu Ile Phe Phe Asn Leu Leu Phe Thr Ser Ala Pro 1145 1150 1155 cct gtc att tat ggt gtt ttg gag aaa gat gtg tct gca gag acc ctc 3797 Pro Val Ile Tyr Gly Val Leu Glu Lys Asp Val Ser Ala Glu Thr Leu 1160 1165 1170 1175 atg caa ctg cct gaa ctt tac aga agt ggt cag aaa tca gag gca tac 3845 Met Gln Leu Pro Glu Leu Tyr Arg Ser Gly Gln Lys Ser Glu Ala Tyr 1180 1185 1190 tta ccc cat acc ttc tgg atc acc tta ttg gat gct ttt tat caa agc 3893 Leu Pro His Thr Phe Trp Ile Thr Leu Leu Asp Ala Phe Tyr Gln Ser 1195 1200 1205 ctg gtc tgc ttc ttt gtg cct tat ttt acc tac cag ggc tca gat act 3941 Leu Val Cys Phe Phe Val Pro Tyr Phe Thr Tyr Gln Gly Ser Asp Thr 1210 1215 1220 gac atc ttt gca ttt gga aac ccc ctg aac aca gcc gct ctg ttc atc 3989 Asp Ile Phe Ala Phe Gly Asn Pro Leu Asn Thr Ala Ala Leu Phe Ile 1225 1230 1235 gtt ctc ctc cat ctg gtc att gaa agc aag agt ttg act tgg att cac 4037 Val Leu Leu His Leu Val Ile Glu Ser Lys Ser Leu Thr Trp Ile His 1240 1245 1250 1255 ttg ctg gtc atc att ggt agc atc ttg tct tat ttt tta ttt gcc ata 4085 Leu Leu Val Ile Ile Gly Ser Ile Leu Ser Tyr Phe Leu Phe Ala Ile 1260 1265 1270 gtt ttt gga gcc atg tgt gta act tgc aac cca cca tcc aac cct tac 4133 Val Phe Gly Ala Met Cys Val Thr Cys Asn Pro Pro Ser Asn Pro Tyr 1275 1280 1285 tgg att atg cag gag cac atg ctg gat cca gta ttc tac tta gtt tgt 4181 Trp Ile Met Gln Glu His Met Leu Asp Pro Val Phe Tyr Leu Val Cys 1290 1295 1300 atc ctc acg acg tcc att gct ctt ctg ccc agg ttt gta tac aga gtt 4229 Ile Leu Thr Thr Ser Ile Ala Leu Leu Pro Arg Phe Val Tyr Arg Val 1305 1310 1315 ctt cag gga tcc ctg ttt cca tct cca att ctg aga gct aag cac ttt 4277 Leu Gln Gly Ser Leu Phe Pro Ser Pro Ile Leu Arg Ala Lys His Phe 1320 1325 1330 1335 gac aga cta act cca gag gag agg act aaa gct ctc aag aag tgg aga 4325 Asp Arg Leu Thr Pro Glu Glu Arg Thr Lys Ala Leu Lys Lys Trp Arg 1340 1345 1350 ggg gct gga aag atg aat caa gtg aca tca aag tat gct aac caa tca 4373 Gly Ala Gly Lys Met Asn Gln Val Thr Ser Lys Tyr Ala Asn Gln Ser 1355 1360 1365 gct ggc aag tca gga aga aga ccc atg cct ggc cct tct gct gta ttt 4421 Ala Gly Lys Ser Gly Arg Arg Pro Met Pro Gly Pro Ser Ala Val Phe 1370 1375 1380 gca atg aag tca gca act tcc tgt gct att gag caa gga aac tta tct 4469 Ala Met Lys Ser Ala Thr Ser Cys Ala Ile Glu Gln Gly Asn Leu Ser 1385 1390 1395 ctg tgt gaa act gct tta gat caa ggc tac tct gaa act aag gcc ttt 4517 Leu Cys Glu Thr Ala Leu Asp Gln Gly Tyr Ser Glu Thr Lys Ala Phe 1400 1405 1410 1415 gag atg gct gga ccc tcc aaa ggt aaa gaa agc tag ataccctcct 4563 Glu Met Ala Gly Pro Ser Lys Gly Lys Glu Ser * 1420 1425 tggagttgca agtattcttt caaggttgga agagggattt tgaagaggta tctctccaag 4623 caagaatgac ttgtttttcc ataagggaca tgagcatttt actaggcttg gaagagctga 4683 catgatgagc attattgtat gtttgtatat acatttgtga tagagggcta gagtttgacc 4743 tagagagagt ttaaggaagt gaaatattta attcagaacc aaatgctttt gtaaaacttt 4803 ttggattttg taaaagcatt ttcattctct tagaaattca agtattttca aggggagtca 4863 tttgagatat atttatttta ctaggagatc ttatattcta gggaaatgct ttaaatggtc 4923 aggctccaat cggaattttt ttaagaaaaa agtagttttt aatacattgg ttaggactca 4983 gaggaaatac ggaaaaaaca ttgtagatgg ttaatttaca gataaaatcc caagagcctt 5043 ttaaacaaca aggtacctaa aatagggtat aattatactg cttaaaatac agttagtgcc 5103 tattaatagc tttttatttc ctatgggaag atgcttttgg tcttctggct gaagatgtag 5163 gcatacctct cactcatttc aatgttttcc tgaggtggag ccttcattgg aaaggggaaa 5223 gagggattct agggtttcat cagggaccag gaatgcattc ctctgtcagg ttccaatcaa 5283 gagaagacct tttatgagat ctgcctctgt atagatgttg tcagttagga aactgaagcc 5343 ataggtcagg cagacatcag ctcagcctgt ggcccattgg gtgatttcct gtattttaaa 5403 actgacagta gcctgatcaa agtgatacaa tcaatttcaa aacaatcttc cagagaccac 5463 ttgaaggttc atagttttta caataccctg agacttttca ggtgttggag cctctaaaat 5523 atgagatata aacagaaact aatacaagtt gttctctgga ggtttctatg aggttcttag 5583 aaaaatttgg ttttaaaatc atttgaggac aggaatgtct atagcaagtt tactcctatt 5643 gcgaatcatg tatgctggct ttagttgtaa caaacgattt tattctaagt aaggccaggt 5703 gctactataa aatcatatat tcctgttgaa gttcttttga agtcctatct ctatttatta 5763 tatttgaaag ttgtcagcca ccagtcatcc agaatttcct tcctgaatct ccatgctcat 5823 atgcaatgtc tacatcaagg tcttcttaat gactattatt ctcagggttt agttttctac 5883 cttctgccta ctattttggt ctgacatttt tgtagccttc tgttattatt ggaaatagtc 5943 tcttacataa gctgatttcg agaactttca aaatctcaca tagctaatgg aagttgcttt 6003 ctgctttctt atgactgttt ttataaataa actgtttcat aaataaaaaa aaaaaaaaaa 6063 gggcggccgc 6073 <210> SEQ ID NO 17 <211> LENGTH: 1426 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 17 Met Thr Glu Ala Leu Gln Trp Ala Arg Tyr His Trp Arg Arg Leu Ile 1 5 10 15 Arg Gly Ala Thr Arg Asp Asp Asp Ser Gly Pro Tyr Asn Tyr Ser Ser 20 25 30 Leu Leu Ala Cys Gly Arg Lys Ser Ser Gln Ile Pro Lys Leu Ser Gly 35 40 45 Arg His Arg Ile Val Val Pro His Ile Gln Pro Phe Lys Asp Glu Tyr 50 55 60 Glu Lys Phe Ser Gly Ala Tyr Val Asn Asn Arg Ile Arg Thr Thr Lys 65 70 75 80 Tyr Thr Leu Leu Asn Phe Val Pro Arg Asn Leu Phe Glu Gln Phe His 85 90 95 Arg Ala Ala Ser Leu Tyr Phe Leu Phe Leu Val Val Leu Asn Trp Val 100 105 110 Pro Leu Val Glu Ala Phe Gln Lys Glu Ile Thr Met Leu Pro Leu Val 115 120 125 Val Val Leu Thr Ile Ile Ala Ile Lys Asp Gly Leu Glu Asp Tyr Arg 130 135 140 Lys Tyr Lys Ile Asp Lys Gln Ile Asn Asn Leu Ile Thr Lys Val Tyr 145 150 155 160 Ser Arg Lys Glu Lys Lys Tyr Ile Asp Arg Cys Trp Lys Asp Val Thr 165 170 175 Val Gly Asp Phe Ile Arg Leu Ser Cys Asn Glu Val Ile Pro Ala Asp 180 185 190 Met Val Leu Leu Phe Ser Thr Asp Pro Asp Gly Ile Cys His Ile Glu 195 200 205 Thr Ser Gly Leu Asp Gly Glu Ser Asn Leu Lys Gln Arg Gln Val Val 210 215 220 Arg Gly Tyr Ala Glu Gln Asp Ser Glu Val Asp Pro Glu Lys Phe Ser 225 230 235 240 Ser Arg Ile Glu Cys Glu Ser Pro Asn Asn Asp Leu Ser Arg Phe Arg 245 250 255 Gly Phe Leu Glu His Ser Asn Lys Glu Arg Val Gly Leu Ser Lys Glu 260 265 270 Asn Leu Leu Leu Arg Gly Cys Thr Ile Arg Asn Thr Glu Ala Val Val 275 280 285 Gly Ile Val Val Tyr Ala Gly His Glu Thr Lys Ala Met Leu Asn Asn 290 295 300 Ser Gly Pro Arg Tyr Lys Arg Ser Lys Leu Glu Arg Arg Ala Asn Thr 305 310 315 320 Asp Val Leu Trp Cys Val Met Leu Leu Val Ile Met Cys Leu Thr Gly 325 330 335 Ala Val Gly His Gly Ile Trp Leu Ser Arg Tyr Glu Lys Met His Phe 340 345 350 Phe Asn Val Pro Glu Pro Asp Gly His Ile Ile Ser Pro Leu Leu Ala 355 360 365 Gly Phe Tyr Met Phe Trp Thr Met Ile Ile Leu Leu Gln Val Leu Ile 370 375 380 Pro Ile Ser Leu Tyr Val Ser Ile Glu Ile Val Lys Leu Gly Gln Ile 385 390 395 400 Tyr Phe Ile Gln Ser Asp Val Asp Phe Tyr Asn Glu Lys Met Asp Ser 405 410 415 Ile Val Gln Cys Arg Ala Leu Asn Ile Ala Glu Asp Leu Gly Gln Ile 420 425 430 Gln Tyr Leu Phe Ser Asp Lys Thr Gly Thr Leu Thr Glu Asn Lys Met 435 440 445 Val Phe Arg Arg Cys Ser Val Ala Gly Phe Asp Tyr Cys His Glu Glu 450 455 460 Asn Ala Arg Arg Leu Glu Ser Tyr Gln Glu Ala Val Ser Glu Asp Glu 465 470 475 480 Asp Phe Ile Asp Thr Val Ser Gly Ser Leu Ser Asn Met Ala Lys Pro 485 490 495 Arg Ala Pro Ser Cys Arg Thr Val His Asn Gly Pro Leu Gly Asn Lys 500 505 510 Pro Ser Asn His Leu Ala Gly Ser Ser Phe Thr Leu Gly Ser Gly Glu 515 520 525 Gly Ala Ser Glu Val Pro His Ser Arg Gln Ala Ala Phe Ser Ser Pro 530 535 540 Ile Glu Thr Asp Val Val Pro Asp Thr Arg Leu Leu Asp Lys Phe Ser 545 550 555 560 Gln Ile Thr Pro Arg Leu Phe Met Pro Leu Asp Glu Thr Ile Gln Asn 565 570 575 Pro Pro Met Glu Thr Leu Tyr Ile Ile Asp Phe Phe Ile Ala Leu Ala 580 585 590 Ile Cys Asn Thr Val Val Val Ser Ala Pro Asn Gln Pro Arg Gln Lys 595 600 605 Ile Arg His Pro Ser Leu Gly Gly Leu Pro Ile Lys Ser Leu Glu Glu 610 615 620 Ile Lys Ser Leu Phe Gln Arg Trp Ser Val Arg Arg Ser Ser Ser Pro 625 630 635 640 Ser Leu Asn Ser Gly Lys Glu Pro Ser Ser Gly Val Pro Asn Ala Phe 645 650 655 Val Ser Arg Leu Pro Leu Phe Ser Arg Met Lys Pro Ala Ser Pro Val 660 665 670 Glu Glu Glu Val Ser Gln Val Cys Glu Ser Pro Gln Cys Ser Ser Ser 675 680 685 Ser Ala Cys Cys Thr Glu Thr Glu Lys Gln His Gly Asp Ala Gly Leu 690 695 700 Leu Asn Gly Lys Ala Glu Ser Leu Pro Gly Gln Pro Leu Ala Cys Asn 705 710 715 720 Leu Cys Tyr Glu Ala Glu Ser Pro Asp Glu Ala Ala Leu Val Tyr Ala 725 730 735 Ala Arg Ala Tyr Gln Cys Thr Leu Arg Ser Arg Thr Pro Glu Gln Val 740 745 750 Met Val Asp Phe Ala Ala Leu Gly Pro Leu Thr Phe Gln Leu Leu His 755 760 765 Ile Leu Pro Phe Asp Ser Val Arg Lys Arg Met Ser Val Val Val Arg 770 775 780 His Pro Leu Ser Asn Gln Val Val Val Tyr Thr Lys Gly Ala Asp Ser 785 790 795 800 Val Ile Met Glu Leu Leu Ser Val Ala Ser Pro Asp Gly Ala Ser Leu 805 810 815 Glu Lys Gln Gln Met Ile Val Arg Glu Lys Thr Gln Lys His Leu Asp 820 825 830 Asp Tyr Ala Lys Gln Gly Leu Arg Thr Leu Cys Ile Ala Lys Lys Val 835 840 845 Met Ser Asp Thr Glu Tyr Ala Glu Trp Leu Arg Asn His Phe Leu Ala 850 855 860 Glu Thr Ser Ile Asp Asn Arg Glu Glu Leu Leu Leu Glu Ser Ala Met 865 870 875 880 Arg Leu Glu Asn Lys Leu Thr Leu Leu Gly Ala Thr Gly Ile Glu Asp 885 890 895 Arg Leu Gln Glu Gly Val Pro Glu Ser Ile Glu Ala Leu His Lys Ala 900 905 910 Gly Ile Lys Ile Trp Met Leu Thr Gly Asp Lys Gln Glu Thr Ala Val 915 920 925 Asn Ile Ala Tyr Ala Cys Lys Leu Leu Glu Pro Asp Asp Lys Leu Phe 930 935 940 Ile Leu Asn Thr Gln Ser Lys Asp Ala Cys Gly Met Leu Met Ser Thr 945 950 955 960 Ile Leu Lys Glu Leu Gln Lys Lys Thr Gln Ala Leu Pro Glu Gln Val 965 970 975 Ser Leu Ser Glu Asp Leu Leu Gln Pro Pro Val Pro Arg Asp Ser Gly 980 985 990 Leu Arg Ala Gly Leu Ile Ile Thr Gly Lys Thr Leu Glu Phe Ala Leu 995 1000 1005 Gln Glu Ser Leu Gln Lys Gln Phe Leu Glu Leu Thr Ser Trp Cys Gln 1010 1015 1020 Ala Val Val Cys Cys Arg Ala Thr Pro Leu Gln Lys Ser Glu Val Val 1025 1030 1035 1040 Lys Leu Val Arg Ser His Leu Gln Val Met Thr Leu Ala Ile Gly Asp 1045 1050 1055 Gly Ala Asn Asp Val Ser Met Ile Gln Val Ala Asp Ile Gly Ile Gly 1060 1065 1070 Val Ser Gly Gln Glu Gly Met Gln Ala Val Met Ala Ser Asp Phe Ala 1075 1080 1085 Val Ser Gln Phe Lys His Leu Ser Lys Leu Leu Leu Val His Gly His 1090 1095 1100 Trp Cys Tyr Thr Arg Leu Ser Asn Met Ile Leu Tyr Phe Phe Tyr Lys 1105 1110 1115 1120 Asn Val Ala Tyr Val Asn Leu Leu Phe Trp Tyr Gln Phe Phe Cys Gly 1125 1130 1135 Phe Ser Gly Thr Ser Met Thr Asp Tyr Trp Val Leu Ile Phe Phe Asn 1140 1145 1150 Leu Leu Phe Thr Ser Ala Pro Pro Val Ile Tyr Gly Val Leu Glu Lys 1155 1160 1165 Asp Val Ser Ala Glu Thr Leu Met Gln Leu Pro Glu Leu Tyr Arg Ser 1170 1175 1180 Gly Gln Lys Ser Glu Ala Tyr Leu Pro His Thr Phe Trp Ile Thr Leu 1185 1190 1195 1200 Leu Asp Ala Phe Tyr Gln Ser Leu Val Cys Phe Phe Val Pro Tyr Phe 1205 1210 1215 Thr Tyr Gln Gly Ser Asp Thr Asp Ile Phe Ala Phe Gly Asn Pro Leu 1220 1225 1230 Asn Thr Ala Ala Leu Phe Ile Val Leu Leu His Leu Val Ile Glu Ser 1235 1240 1245 Lys Ser Leu Thr Trp Ile His Leu Leu Val Ile Ile Gly Ser Ile Leu 1250 1255 1260 Ser Tyr Phe Leu Phe Ala Ile Val Phe Gly Ala Met Cys Val Thr Cys 1265 1270 1275 1280 Asn Pro Pro Ser Asn Pro Tyr Trp Ile Met Gln Glu His Met Leu Asp 1285 1290 1295 Pro Val Phe Tyr Leu Val Cys Ile Leu Thr Thr Ser Ile Ala Leu Leu 1300 1305 1310 Pro Arg Phe Val Tyr Arg Val Leu Gln Gly Ser Leu Phe Pro Ser Pro 1315 1320 1325 Ile Leu Arg Ala Lys His Phe Asp Arg Leu Thr Pro Glu Glu Arg Thr 1330 1335 1340 Lys Ala Leu Lys Lys Trp Arg Gly Ala Gly Lys Met Asn Gln Val Thr 1345 1350 1355 1360 Ser Lys Tyr Ala Asn Gln Ser Ala Gly Lys Ser Gly Arg Arg Pro Met 1365 1370 1375 Pro Gly Pro Ser Ala Val Phe Ala Met Lys Ser Ala Thr Ser Cys Ala 1380 1385 1390 Ile Glu Gln Gly Asn Leu Ser Leu Cys Glu Thr Ala Leu Asp Gln Gly 1395 1400 1405 Tyr Ser Glu Thr Lys Ala Phe Glu Met Ala Gly Pro Ser Lys Gly Lys 1410 1415 1420 Glu Ser 1425 <210> SEQ ID NO 18 <211> LENGTH: 4281 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(4281) <400> SEQUENCE: 18 atg act gag gct ctc caa tgg gcc aga tat cac tgg cga cgg ctg atc 48 Met Thr Glu Ala Leu Gln Trp Ala Arg Tyr His Trp Arg Arg Leu Ile 1 5 10 15 aga ggt gca acc agg gat gat gat tca ggg cca tac aac tat tcc tcg 96 Arg Gly Ala Thr Arg Asp Asp Asp Ser Gly Pro Tyr Asn Tyr Ser Ser 20 25 30 ttg ctc gcc tgt ggg cgc aag tcc tct cag atc cct aaa ctg tca gga 144 Leu Leu Ala Cys Gly Arg Lys Ser Ser Gln Ile Pro Lys Leu Ser Gly 35 40 45 agg cac cgg att gtt gtt ccc cac atc cag ccc ttc aag gat gag tat 192 Arg His Arg Ile Val Val Pro His Ile Gln Pro Phe Lys Asp Glu Tyr 50 55 60 gag aag ttc tcc gga gcc tat gtg aac aat cga ata cga aca aca aag 240 Glu Lys Phe Ser Gly Ala Tyr Val Asn Asn Arg Ile Arg Thr Thr Lys 65 70 75 80 tac aca ctt ctg aat ttt gtg cca aga aat tta ttt gaa caa ttt cac 288 Tyr Thr Leu Leu Asn Phe Val Pro Arg Asn Leu Phe Glu Gln Phe His 85 90 95 aga gct gcc agt tta tat ttc ctg ttc cta gtt gtc ctg aac tgg gta 336 Arg Ala Ala Ser Leu Tyr Phe Leu Phe Leu Val Val Leu Asn Trp Val 100 105 110 cct ttg gta gaa gcc ttc caa aag gaa atc acc atg ttg cct ctg gtg 384 Pro Leu Val Glu Ala Phe Gln Lys Glu Ile Thr Met Leu Pro Leu Val 115 120 125 gtg gtc ctt aca att atc gca att aaa gat ggc ctg gaa gat tat cgg 432 Val Val Leu Thr Ile Ile Ala Ile Lys Asp Gly Leu Glu Asp Tyr Arg 130 135 140 aaa tac aaa att gac aaa cag atc aat aat tta ata act aaa gtt tat 480 Lys Tyr Lys Ile Asp Lys Gln Ile Asn Asn Leu Ile Thr Lys Val Tyr 145 150 155 160 agt agg aaa gag aaa aaa tac att gac cga tgc tgg aaa gac gtt act 528 Ser Arg Lys Glu Lys Lys Tyr Ile Asp Arg Cys Trp Lys Asp Val Thr 165 170 175 gtt ggg gac ttt att cgc ctc tcc tgc aat gag gtc atc cct gca gac 576 Val Gly Asp Phe Ile Arg Leu Ser Cys Asn Glu Val Ile Pro Ala Asp 180 185 190 atg gta cta ctc ttt tcc act gat cca gat gga atc tgt cac att gag 624 Met Val Leu Leu Phe Ser Thr Asp Pro Asp Gly Ile Cys His Ile Glu 195 200 205 act tct ggt ctt gat gga gag agc aat tta aaa cag agg cag gtg gtt 672 Thr Ser Gly Leu Asp Gly Glu Ser Asn Leu Lys Gln Arg Gln Val Val 210 215 220 cgg gga tat gca gaa cag gac tct gaa gtt gat cct gag aag ttt tcc 720 Arg Gly Tyr Ala Glu Gln Asp Ser Glu Val Asp Pro Glu Lys Phe Ser 225 230 235 240 agt agg ata gaa tgt gaa agc cca aac aat gac ctc agc aga ttc cga 768 Ser Arg Ile Glu Cys Glu Ser Pro Asn Asn Asp Leu Ser Arg Phe Arg 245 250 255 ggc ttc cta gaa cat tcc aac aaa gaa cgc gtg ggt ctc agt aaa gaa 816 Gly Phe Leu Glu His Ser Asn Lys Glu Arg Val Gly Leu Ser Lys Glu 260 265 270 aat ttg ttg ctt aga gga tgc acc att aga aac aca gag gct gtt gtg 864 Asn Leu Leu Leu Arg Gly Cys Thr Ile Arg Asn Thr Glu Ala Val Val 275 280 285 ggc att gtg gtt tat gca ggc cat gaa acc aaa gca atg ctg aac aac 912 Gly Ile Val Val Tyr Ala Gly His Glu Thr Lys Ala Met Leu Asn Asn 290 295 300 agt ggg cca cgg tat aag cgc agc aaa tta gaa aga aga gca aac aca 960 Ser Gly Pro Arg Tyr Lys Arg Ser Lys Leu Glu Arg Arg Ala Asn Thr 305 310 315 320 gat gtc ctc tgg tgt gtc atg ctt ctg gtc ata atg tgc tta act ggc 1008 Asp Val Leu Trp Cys Val Met Leu Leu Val Ile Met Cys Leu Thr Gly 325 330 335 gca gta ggt cat gga atc tgg ctg agc agg tat gaa aag atg cat ttt 1056 Ala Val Gly His Gly Ile Trp Leu Ser Arg Tyr Glu Lys Met His Phe 340 345 350 ttc aat gtt ccc gag cct gat gga cat atc ata tca cca ctg ttg gca 1104 Phe Asn Val Pro Glu Pro Asp Gly His Ile Ile Ser Pro Leu Leu Ala 355 360 365 gga ttt tat atg ttt tgg acc atg atc att ttg tta cag gtc ttg att 1152 Gly Phe Tyr Met Phe Trp Thr Met Ile Ile Leu Leu Gln Val Leu Ile 370 375 380 cct att tct ctc tat gtt tcc atc gaa att gtg aag ctt gga caa ata 1200 Pro Ile Ser Leu Tyr Val Ser Ile Glu Ile Val Lys Leu Gly Gln Ile 385 390 395 400 tat ttc att caa agt gat gtg gat ttc tac aat gaa aaa atg gat tct 1248 Tyr Phe Ile Gln Ser Asp Val Asp Phe Tyr Asn Glu Lys Met Asp Ser 405 410 415 att gtt cag tgc cga gcc ctg aac atc gcc gag gat ctg gga cag att 1296 Ile Val Gln Cys Arg Ala Leu Asn Ile Ala Glu Asp Leu Gly Gln Ile 420 425 430 cag tac ctc ttt tcc gat aag aca gga acc ctc act gag aat aag atg 1344 Gln Tyr Leu Phe Ser Asp Lys Thr Gly Thr Leu Thr Glu Asn Lys Met 435 440 445 gtt ttt cga aga tgt agt gtg gca gga ttt gat tac tgc cat gaa gaa 1392 Val Phe Arg Arg Cys Ser Val Ala Gly Phe Asp Tyr Cys His Glu Glu 450 455 460 aat gcc agg agg ttg gag tcc tat cag gaa gct gtc tct gaa gat gaa 1440 Asn Ala Arg Arg Leu Glu Ser Tyr Gln Glu Ala Val Ser Glu Asp Glu 465 470 475 480 gat ttt ata gac aca gtc agt ggt tcc ctc agc aat atg gca aaa ccg 1488 Asp Phe Ile Asp Thr Val Ser Gly Ser Leu Ser Asn Met Ala Lys Pro 485 490 495 aga gcc ccc agc tgc agg aca gtt cat aat ggg cct ttg gga aat aag 1536 Arg Ala Pro Ser Cys Arg Thr Val His Asn Gly Pro Leu Gly Asn Lys 500 505 510 ccc tca aat cat ctt gct ggg agc tct ttt act cta gga agt gga gaa 1584 Pro Ser Asn His Leu Ala Gly Ser Ser Phe Thr Leu Gly Ser Gly Glu 515 520 525 gga gcc agt gaa gtg cct cat tcc aga cag gct gct ttc agt agc ccc 1632 Gly Ala Ser Glu Val Pro His Ser Arg Gln Ala Ala Phe Ser Ser Pro 530 535 540 att gaa aca gac gtg gta cca gac acc agg ctt tta gac aaa ttt agt 1680 Ile Glu Thr Asp Val Val Pro Asp Thr Arg Leu Leu Asp Lys Phe Ser 545 550 555 560 cag att aca cct cgg ctc ttt atg cca cta gat gag acc atc caa aat 1728 Gln Ile Thr Pro Arg Leu Phe Met Pro Leu Asp Glu Thr Ile Gln Asn 565 570 575 cca cca atg gaa act ttg tac att atc gac ttt ttc att gca ttg gca 1776 Pro Pro Met Glu Thr Leu Tyr Ile Ile Asp Phe Phe Ile Ala Leu Ala 580 585 590 att tgc aac aca gta gtg gtt tct gct cct aac caa ccc cga caa aag 1824 Ile Cys Asn Thr Val Val Val Ser Ala Pro Asn Gln Pro Arg Gln Lys 595 600 605 atc aga cac cct tca ctg ggg ggg ttg ccc att aag tct ttg gaa gag 1872 Ile Arg His Pro Ser Leu Gly Gly Leu Pro Ile Lys Ser Leu Glu Glu 610 615 620 att aaa agt ctt ttc cag aga tgg tct gtc cga aga tca agt tct cca 1920 Ile Lys Ser Leu Phe Gln Arg Trp Ser Val Arg Arg Ser Ser Ser Pro 625 630 635 640 tcg ctt aac agt ggg aaa gag cca tct tct gga gtt cca aac gcc ttt 1968 Ser Leu Asn Ser Gly Lys Glu Pro Ser Ser Gly Val Pro Asn Ala Phe 645 650 655 gtg agc aga ctc cct ctc ttt agt cga atg aaa cca gct tca cct gtg 2016 Val Ser Arg Leu Pro Leu Phe Ser Arg Met Lys Pro Ala Ser Pro Val 660 665 670 gag gaa gag gtc tcc cag gtg tgt gag agc ccc cag tgc tcc agt agc 2064 Glu Glu Glu Val Ser Gln Val Cys Glu Ser Pro Gln Cys Ser Ser Ser 675 680 685 tca gct tgc tgc aca gaa aca gag aaa caa cac ggt gat gca ggc ctc 2112 Ser Ala Cys Cys Thr Glu Thr Glu Lys Gln His Gly Asp Ala Gly Leu 690 695 700 ctg aat ggc aag gca gag tcc ctc cct gga cag cca ttg gcc tgc aac 2160 Leu Asn Gly Lys Ala Glu Ser Leu Pro Gly Gln Pro Leu Ala Cys Asn 705 710 715 720 ctg tgt tat gag gcc gag agc cca gac gaa gcg gcc tta gtg tat gcc 2208 Leu Cys Tyr Glu Ala Glu Ser Pro Asp Glu Ala Ala Leu Val Tyr Ala 725 730 735 gcc agg gct tac caa tgc act tta cgg tct cgg aca cca gag cag gtc 2256 Ala Arg Ala Tyr Gln Cys Thr Leu Arg Ser Arg Thr Pro Glu Gln Val 740 745 750 atg gtg gac ttt gct gct ttg gga cca tta aca ttt caa ctc cta cac 2304 Met Val Asp Phe Ala Ala Leu Gly Pro Leu Thr Phe Gln Leu Leu His 755 760 765 atc ctg ccc ttt gac tca gta aga aaa aga atg tct gtt gtg gtc cga 2352 Ile Leu Pro Phe Asp Ser Val Arg Lys Arg Met Ser Val Val Val Arg 770 775 780 cac cct ctt tcc aat caa gtt gtg gtg tat acg aaa ggc gct gat tct 2400 His Pro Leu Ser Asn Gln Val Val Val Tyr Thr Lys Gly Ala Asp Ser 785 790 795 800 gtg atc atg gag tta ctg tcg gtg gct tcc cca gat gga gca agt ctg 2448 Val Ile Met Glu Leu Leu Ser Val Ala Ser Pro Asp Gly Ala Ser Leu 805 810 815 gag aaa caa cag atg ata gta agg gag aaa acc cag aag cac ttg gat 2496 Glu Lys Gln Gln Met Ile Val Arg Glu Lys Thr Gln Lys His Leu Asp 820 825 830 gac tat gcc aaa caa ggc ctt cgt act tta tgt ata gca aag aag gtc 2544 Asp Tyr Ala Lys Gln Gly Leu Arg Thr Leu Cys Ile Ala Lys Lys Val 835 840 845 atg agt gac act gaa tat gca gag tgg ctg agg aat cat ttt tta gct 2592 Met Ser Asp Thr Glu Tyr Ala Glu Trp Leu Arg Asn His Phe Leu Ala 850 855 860 gaa acc agc att gac aac agg gaa gaa tta cta ctt gaa tct gcc atg 2640 Glu Thr Ser Ile Asp Asn Arg Glu Glu Leu Leu Leu Glu Ser Ala Met 865 870 875 880 agg ttg gag aac aaa ctt aca tta ctt ggt gct act ggc att gaa gac 2688 Arg Leu Glu Asn Lys Leu Thr Leu Leu Gly Ala Thr Gly Ile Glu Asp 885 890 895 cgt ctg cag gag gga gtc cct gaa tct ata gaa gct ctt cac aaa gcg 2736 Arg Leu Gln Glu Gly Val Pro Glu Ser Ile Glu Ala Leu His Lys Ala 900 905 910 ggc atc aag atc tgg atg ctg aca ggg gac aag cag gag aca gct gtc 2784 Gly Ile Lys Ile Trp Met Leu Thr Gly Asp Lys Gln Glu Thr Ala Val 915 920 925 aac ata gct tat gca tgc aaa cta ctg gag cca gat gac aag ctt ttt 2832 Asn Ile Ala Tyr Ala Cys Lys Leu Leu Glu Pro Asp Asp Lys Leu Phe 930 935 940 atc ctc aat acc caa agt aaa gat gcc tgt ggg atg ctg atg agc aca 2880 Ile Leu Asn Thr Gln Ser Lys Asp Ala Cys Gly Met Leu Met Ser Thr 945 950 955 960 att ttg aaa gaa ctt cag aag aaa act caa gcc ctg cca gag caa gtg 2928 Ile Leu Lys Glu Leu Gln Lys Lys Thr Gln Ala Leu Pro Glu Gln Val 965 970 975 tca tta agt gaa gat tta ctt cag cct cct gtc ccc cgg gac tca ggg 2976 Ser Leu Ser Glu Asp Leu Leu Gln Pro Pro Val Pro Arg Asp Ser Gly 980 985 990 tta cga gct gga ctc att atc act ggg aag acc ctg gag ttt gcc ctg 3024 Leu Arg Ala Gly Leu Ile Ile Thr Gly Lys Thr Leu Glu Phe Ala Leu 995 1000 1005 caa gaa agt ctg caa aag cag ttc ctg gaa ctg aca tct tgg tgt caa 3072 Gln Glu Ser Leu Gln Lys Gln Phe Leu Glu Leu Thr Ser Trp Cys Gln 1010 1015 1020 gct gtg gtc tgc tgc cga gcc aca ccg ctg cag aaa agt gaa gtg gtg 3120 Ala Val Val Cys Cys Arg Ala Thr Pro Leu Gln Lys Ser Glu Val Val 1025 1030 1035 1040 aaa ttg gtc cgc agc cat ctc cag gtg atg acc ctt gct att ggt gat 3168 Lys Leu Val Arg Ser His Leu Gln Val Met Thr Leu Ala Ile Gly Asp 1045 1050 1055 ggt gcc aat gat gtt agc atg ata caa gtg gca gac att ggg ata ggg 3216 Gly Ala Asn Asp Val Ser Met Ile Gln Val Ala Asp Ile Gly Ile Gly 1060 1065 1070 gtc tca ggt caa gaa ggc atg cag gct gtg atg gcc agt gac ttt gcc 3264 Val Ser Gly Gln Glu Gly Met Gln Ala Val Met Ala Ser Asp Phe Ala 1075 1080 1085 gtt tct cag ttc aaa cat ctc agc aag ctc ctt ctt gtc cat gga cac 3312 Val Ser Gln Phe Lys His Leu Ser Lys Leu Leu Leu Val His Gly His 1090 1095 1100 tgg tgt tat aca cgg ctt tcc aac atg att ctc tat ttt ttc tat aag 3360 Trp Cys Tyr Thr Arg Leu Ser Asn Met Ile Leu Tyr Phe Phe Tyr Lys 1105 1110 1115 1120 aat gtg gcc tat gtg aac ctc ctt ttc tgg tac cag ttc ttt tgt gga 3408 Asn Val Ala Tyr Val Asn Leu Leu Phe Trp Tyr Gln Phe Phe Cys Gly 1125 1130 1135 ttt tca gga aca tcc atg act gat tac tgg gtt ttg atc ttc ttc aac 3456 Phe Ser Gly Thr Ser Met Thr Asp Tyr Trp Val Leu Ile Phe Phe Asn 1140 1145 1150 ctc ctc ttc aca tct gcc cct cct gtc att tat ggt gtt ttg gag aaa 3504 Leu Leu Phe Thr Ser Ala Pro Pro Val Ile Tyr Gly Val Leu Glu Lys 1155 1160 1165 gat gtg tct gca gag acc ctc atg caa ctg cct gaa ctt tac aga agt 3552 Asp Val Ser Ala Glu Thr Leu Met Gln Leu Pro Glu Leu Tyr Arg Ser 1170 1175 1180 ggt cag aaa tca gag gca tac tta ccc cat acc ttc tgg atc acc tta 3600 Gly Gln Lys Ser Glu Ala Tyr Leu Pro His Thr Phe Trp Ile Thr Leu 1185 1190 1195 1200 ttg gat gct ttt tat caa agc ctg gtc tgc ttc ttt gtg cct tat ttt 3648 Leu Asp Ala Phe Tyr Gln Ser Leu Val Cys Phe Phe Val Pro Tyr Phe 1205 1210 1215 acc tac cag ggc tca gat act gac atc ttt gca ttt gga aac ccc ctg 3696 Thr Tyr Gln Gly Ser Asp Thr Asp Ile Phe Ala Phe Gly Asn Pro Leu 1220 1225 1230 aac aca gcc gct ctg ttc atc gtt ctc ctc cat ctg gtc att gaa agc 3744 Asn Thr Ala Ala Leu Phe Ile Val Leu Leu His Leu Val Ile Glu Ser 1235 1240 1245 aag agt ttg act tgg att cac ttg ctg gtc atc att ggt agc atc ttg 3792 Lys Ser Leu Thr Trp Ile His Leu Leu Val Ile Ile Gly Ser Ile Leu 1250 1255 1260 tct tat ttt tta ttt gcc ata gtt ttt gga gcc atg tgt gta act tgc 3840 Ser Tyr Phe Leu Phe Ala Ile Val Phe Gly Ala Met Cys Val Thr Cys 1265 1270 1275 1280 aac cca cca tcc aac cct tac tgg att atg cag gag cac atg ctg gat 3888 Asn Pro Pro Ser Asn Pro Tyr Trp Ile Met Gln Glu His Met Leu Asp 1285 1290 1295 cca gta ttc tac tta gtt tgt atc ctc acg acg tcc att gct ctt ctg 3936 Pro Val Phe Tyr Leu Val Cys Ile Leu Thr Thr Ser Ile Ala Leu Leu 1300 1305 1310 ccc agg ttt gta tac aga gtt ctt cag gga tcc ctg ttt cca tct cca 3984 Pro Arg Phe Val Tyr Arg Val Leu Gln Gly Ser Leu Phe Pro Ser Pro 1315 1320 1325 att ctg aga gct aag cac ttt gac aga cta act cca gag gag agg act 4032 Ile Leu Arg Ala Lys His Phe Asp Arg Leu Thr Pro Glu Glu Arg Thr 1330 1335 1340 aaa gct ctc aag aag tgg aga ggg gct gga aag atg aat caa gtg aca 4080 Lys Ala Leu Lys Lys Trp Arg Gly Ala Gly Lys Met Asn Gln Val Thr 1345 1350 1355 1360 tca aag tat gct aac caa tca gct ggc aag tca gga aga aga ccc atg 4128 Ser Lys Tyr Ala Asn Gln Ser Ala Gly Lys Ser Gly Arg Arg Pro Met 1365 1370 1375 cct ggc cct tct gct gta ttt gca atg aag tca gca act tcc tgt gct 4176 Pro Gly Pro Ser Ala Val Phe Ala Met Lys Ser Ala Thr Ser Cys Ala 1380 1385 1390 att gag caa gga aac tta tct ctg tgt gaa act gct tta gat caa ggc 4224 Ile Glu Gln Gly Asn Leu Ser Leu Cys Glu Thr Ala Leu Asp Gln Gly 1395 1400 1405 tac tct gaa act aag gcc ttt gag atg gct gga ccc tcc aaa ggt aaa 4272 Tyr Ser Glu Thr Lys Ala Phe Glu Met Ala Gly Pro Ser Lys Gly Lys 1410 1415 1420 gaa agc tag 4281 Glu Ser * 1425 <210> SEQ ID NO 19 <211> LENGTH: 7221 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (167)...(3700) <400> SEQUENCE: 19 gccgcgggat gggaacgcgg cgcggggagt gaggcagtgg cggcggcggc ggtaagcgga 60 acttcggccc gaggggctcg cccgctcccg cctctgtctt gtcggcctcc acctgcagcc 120 ccgcggcccc cgcgccccgc gggacccgga cggcgacgac ggggga atg tgg cgc 175 Met Trp Arg 1 tgg atc cgg cag cag ctg ggt ttt gac cca cca cat cag agt gac aca 223 Trp Ile Arg Gln Gln Leu Gly Phe Asp Pro Pro His Gln Ser Asp Thr 5 10 15 aga acc atc tac gta gcc cac agg ttt cct cag aat ggc ctt tac aca 271 Arg Thr Ile Tyr Val Ala His Arg Phe Pro Gln Asn Gly Leu Tyr Thr 20 25 30 35 cct cag aaa ttt ata gat aac agg atc att tca tct aag tac act gtg 319 Pro Gln Lys Phe Ile Asp Asn Arg Ile Ile Ser Ser Lys Tyr Thr Val 40 45 50 tgg aat ttt gtt cca aaa aat tta ttt gaa cag ttc aga aga gtg gca 367 Trp Asn Phe Val Pro Lys Asn Leu Phe Glu Gln Phe Arg Arg Val Ala 55 60 65 aac ttt tat ttt ctt att ata ttt ttg gtt cag ctt atg att gat aca 415 Asn Phe Tyr Phe Leu Ile Ile Phe Leu Val Gln Leu Met Ile Asp Thr 70 75 80 cct acc agt cca gtt acc agt gga ctt cca tta ttc ttt gtg ata aca 463 Pro Thr Ser Pro Val Thr Ser Gly Leu Pro Leu Phe Phe Val Ile Thr 85 90 95 gta act gcc ata aag cag gga tat gaa gat tgg tta cgg cat aac tca 511 Val Thr Ala Ile Lys Gln Gly Tyr Glu Asp Trp Leu Arg His Asn Ser 100 105 110 115 gat aat gaa gta aat gga gct cct gtt tat gtt gtt cga agt ggt ggc 559 Asp Asn Glu Val Asn Gly Ala Pro Val Tyr Val Val Arg Ser Gly Gly 120 125 130 ctt gta aaa act aga tca aaa aac att cgg gtg ggt gat att gtt cga 607 Leu Val Lys Thr Arg Ser Lys Asn Ile Arg Val Gly Asp Ile Val Arg 135 140 145 ata gcc aaa gat gaa att ttt cct gca gac ttg gtg ctt ctg tcc tca 655 Ile Ala Lys Asp Glu Ile Phe Pro Ala Asp Leu Val Leu Leu Ser Ser 150 155 160 gat cga ctg gat ggt tcc tgt cac gtt aca act gct agt ttg gac gga 703 Asp Arg Leu Asp Gly Ser Cys His Val Thr Thr Ala Ser Leu Asp Gly 165 170 175 gaa act aac ctg aag aca cat gtg gca gtt cca gaa aca gca tta tta 751 Glu Thr Asn Leu Lys Thr His Val Ala Val Pro Glu Thr Ala Leu Leu 180 185 190 195 caa aca gtt gcc aat ttg gac act cta gta gct gta ata gaa tgc cag 799 Gln Thr Val Ala Asn Leu Asp Thr Leu Val Ala Val Ile Glu Cys Gln 200 205 210 caa cca gaa gca gac tta tac aga ttc atg gga cga atg atc ata acc 847 Gln Pro Glu Ala Asp Leu Tyr Arg Phe Met Gly Arg Met Ile Ile Thr 215 220 225 caa caa atg gaa gaa att gta aga cct ctg ggg ccg gag agt ctc ctg 895 Gln Gln Met Glu Glu Ile Val Arg Pro Leu Gly Pro Glu Ser Leu Leu 230 235 240 ctt cgt gga gcc aga tta aaa aac aca aaa gaa att ttt ggt gtt gcg 943 Leu Arg Gly Ala Arg Leu Lys Asn Thr Lys Glu Ile Phe Gly Val Ala 245 250 255 gta tac act gga atg gaa act aag atg gca tta aat tac aag agc aaa 991 Val Tyr Thr Gly Met Glu Thr Lys Met Ala Leu Asn Tyr Lys Ser Lys 260 265 270 275 tca cag aaa cga tct gca gta gaa aag tca atg aat aca ttt ttg ata 1039 Ser Gln Lys Arg Ser Ala Val Glu Lys Ser Met Asn Thr Phe Leu Ile 280 285 290 att tat cta gta att ctt ata tct gaa gct gtc atc agc act atc ttg 1087 Ile Tyr Leu Val Ile Leu Ile Ser Glu Ala Val Ile Ser Thr Ile Leu 295 300 305 aag tat aca tgg caa gct gaa gaa aaa tgg gat gaa cct tgg tat aac 1135 Lys Tyr Thr Trp Gln Ala Glu Glu Lys Trp Asp Glu Pro Trp Tyr Asn 310 315 320 caa aaa aca gaa cat caa aga aat agc agt aag att ctg aga ttt att 1183 Gln Lys Thr Glu His Gln Arg Asn Ser Ser Lys Ile Leu Arg Phe Ile 325 330 335 tca gac ttc ctt gct ttt ttg gtt ctc tac aat ttc atc att cca att 1231 Ser Asp Phe Leu Ala Phe Leu Val Leu Tyr Asn Phe Ile Ile Pro Ile 340 345 350 355 tca tta tat gtg aca gtc gaa atg cag aaa ttt ctt gga tca ttt ttt 1279 Ser Leu Tyr Val Thr Val Glu Met Gln Lys Phe Leu Gly Ser Phe Phe 360 365 370 att ggc tgg gat ctt gat ctg tat cat gaa gaa tca gat cag aaa gct 1327 Ile Gly Trp Asp Leu Asp Leu Tyr His Glu Glu Ser Asp Gln Lys Ala 375 380 385 caa gtc aat act tcc gat ctg aat gaa gag ctt gga cag gta gag tac 1375 Gln Val Asn Thr Ser Asp Leu Asn Glu Glu Leu Gly Gln Val Glu Tyr 390 395 400 gtg ttt aca gat aaa act ggt aca ctg aca gaa aat gag atg cag ttt 1423 Val Phe Thr Asp Lys Thr Gly Thr Leu Thr Glu Asn Glu Met Gln Phe 405 410 415 cgg gaa tgt tca att aat ggc atg aaa tac caa gaa att aat ggt aga 1471 Arg Glu Cys Ser Ile Asn Gly Met Lys Tyr Gln Glu Ile Asn Gly Arg 420 425 430 435 ctt gta ccc gaa gga cca aca cca gac tct tca gaa gga aac tta tct 1519 Leu Val Pro Glu Gly Pro Thr Pro Asp Ser Ser Glu Gly Asn Leu Ser 440 445 450 tat ctt agt agt tta tcc cat ctt aac aac tta tcc cat ctt aca acc 1567 Tyr Leu Ser Ser Leu Ser His Leu Asn Asn Leu Ser His Leu Thr Thr 455 460 465 agt tcc tct ttc aga acc agt cct gaa aat gaa act gaa cta att aaa 1615 Ser Ser Ser Phe Arg Thr Ser Pro Glu Asn Glu Thr Glu Leu Ile Lys 470 475 480 gaa cat gat ctc ttc ttt aaa gca gtc agt ctc tgt cac act gta cag 1663 Glu His Asp Leu Phe Phe Lys Ala Val Ser Leu Cys His Thr Val Gln 485 490 495 att agc aat gtt caa act gac tgc act ggt gat ggt ccc tgg caa tcc 1711 Ile Ser Asn Val Gln Thr Asp Cys Thr Gly Asp Gly Pro Trp Gln Ser 500 505 510 515 aac ctg gca cca tcg cag ttg gag tac tat gca tct tca cca gat gaa 1759 Asn Leu Ala Pro Ser Gln Leu Glu Tyr Tyr Ala Ser Ser Pro Asp Glu 520 525 530 aag gct cta gta gaa gct gct gca agg att ggt att gtg ttt att ggc 1807 Lys Ala Leu Val Glu Ala Ala Ala Arg Ile Gly Ile Val Phe Ile Gly 535 540 545 aat tct gaa gaa act atg gag gtt aaa act ctt gga aaa ctg gaa cgg 1855 Asn Ser Glu Glu Thr Met Glu Val Lys Thr Leu Gly Lys Leu Glu Arg 550 555 560 tac aaa ctg ctt cat att ctg gaa ttt gat tca gat cgt agg aga atg 1903 Tyr Lys Leu Leu His Ile Leu Glu Phe Asp Ser Asp Arg Arg Arg Met 565 570 575 agt gta att gtt cag gca cct tca ggt gag aag tta tta ttt gct aaa 1951 Ser Val Ile Val Gln Ala Pro Ser Gly Glu Lys Leu Leu Phe Ala Lys 580 585 590 595 gga gct gag tca tca att ctc cct aaa tgt ata ggt gga gaa ata gaa 1999 Gly Ala Glu Ser Ser Ile Leu Pro Lys Cys Ile Gly Gly Glu Ile Glu 600 605 610 aaa acc aga att cat gta gat gaa ttt gct ttg aaa ggg cta aga act 2047 Lys Thr Arg Ile His Val Asp Glu Phe Ala Leu Lys Gly Leu Arg Thr 615 620 625 ctg tgt ata gca tat aga aaa ttt aca tca aaa gag tat gag gaa ata 2095 Leu Cys Ile Ala Tyr Arg Lys Phe Thr Ser Lys Glu Tyr Glu Glu Ile 630 635 640 gat aaa cgc ata ttt gaa gcc agg act gcc ttg cag cag cgg gaa gag 2143 Asp Lys Arg Ile Phe Glu Ala Arg Thr Ala Leu Gln Gln Arg Glu Glu 645 650 655 aaa ttg gca gct gtt ttc cag ttc ata gag aaa gac ctg ata tta ctt 2191 Lys Leu Ala Ala Val Phe Gln Phe Ile Glu Lys Asp Leu Ile Leu Leu 660 665 670 675 gga gcc aca gca gta gaa gac aga cta caa gat aaa gtt cga gaa act 2239 Gly Ala Thr Ala Val Glu Asp Arg Leu Gln Asp Lys Val Arg Glu Thr 680 685 690 att gaa gca ttg aga atg gct ggt atc aaa gta tgg gta ctt act ggg 2287 Ile Glu Ala Leu Arg Met Ala Gly Ile Lys Val Trp Val Leu Thr Gly 695 700 705 gat aaa cat gaa aca gct gtt agt gtg agt tta tca tgt ggc cat ttt 2335 Asp Lys His Glu Thr Ala Val Ser Val Ser Leu Ser Cys Gly His Phe 710 715 720 cat aga acc atg aac atc ctt gaa ctt ata aac cag aaa tca gac agc 2383 His Arg Thr Met Asn Ile Leu Glu Leu Ile Asn Gln Lys Ser Asp Ser 725 730 735 gag tgt gct gaa caa ttg agg cag ctt gcc aga aga att aca gag gat 2431 Glu Cys Ala Glu Gln Leu Arg Gln Leu Ala Arg Arg Ile Thr Glu Asp 740 745 750 755 cat gtg att cag cat ggg ctg gta gtg gat ggg acc agc cta tct ctt 2479 His Val Ile Gln His Gly Leu Val Val Asp Gly Thr Ser Leu Ser Leu 760 765 770 gca ctc agg gag cat gaa aaa cta ttt atg gaa gtt tgc aga aat tgt 2527 Ala Leu Arg Glu His Glu Lys Leu Phe Met Glu Val Cys Arg Asn Cys 775 780 785 tca gct gta tta tgc tgt cgt atg gct cca ctg cag aaa gca aaa gta 2575 Ser Ala Val Leu Cys Cys Arg Met Ala Pro Leu Gln Lys Ala Lys Val 790 795 800 ata aga cta ata aaa ata tca cct gag aaa cct ata aca ttg gct gtt 2623 Ile Arg Leu Ile Lys Ile Ser Pro Glu Lys Pro Ile Thr Leu Ala Val 805 810 815 ggt gat ggt gct aat gac gta agc atg ata caa gaa gcc cat gtt ggc 2671 Gly Asp Gly Ala Asn Asp Val Ser Met Ile Gln Glu Ala His Val Gly 820 825 830 835 ata gga atc atg ggt aaa gaa gga aga cag gct gca aga aac agt gac 2719 Ile Gly Ile Met Gly Lys Glu Gly Arg Gln Ala Ala Arg Asn Ser Asp 840 845 850 tat gca ata gcc aga ttt aag ttc ctc tcc aaa ttg ctt ttt gtt cat 2767 Tyr Ala Ile Ala Arg Phe Lys Phe Leu Ser Lys Leu Leu Phe Val His 855 860 865 ggt cat ttt tat tat att aga ata gct acc ctt gta cag tat ttt ttt 2815 Gly His Phe Tyr Tyr Ile Arg Ile Ala Thr Leu Val Gln Tyr Phe Phe 870 875 880 tat aag aat gtg tgc ttt atc aca ccc cag ttt tta tat cag ttc tac 2863 Tyr Lys Asn Val Cys Phe Ile Thr Pro Gln Phe Leu Tyr Gln Phe Tyr 885 890 895 tgt ttg ttt tct cag caa aca ttg tat gac agc gtg tac ctg act tta 2911 Cys Leu Phe Ser Gln Gln Thr Leu Tyr Asp Ser Val Tyr Leu Thr Leu 900 905 910 915 tac aat att tgt ttt act tcc cta cct att ctg ata tat agt ctt ttg 2959 Tyr Asn Ile Cys Phe Thr Ser Leu Pro Ile Leu Ile Tyr Ser Leu Leu 920 925 930 gaa cag cat gta gac cct cat gtg tta caa aat aag ccc acc ctt tat 3007 Glu Gln His Val Asp Pro His Val Leu Gln Asn Lys Pro Thr Leu Tyr 935 940 945 cga gac att agt aaa aac cgc ctc tta agt att aaa aca ttt ctt tat 3055 Arg Asp Ile Ser Lys Asn Arg Leu Leu Ser Ile Lys Thr Phe Leu Tyr 950 955 960 tgg acc atc ctg ggc ttc agt cat gcc ttt att ttc ttt ttt gga tcc 3103 Trp Thr Ile Leu Gly Phe Ser His Ala Phe Ile Phe Phe Phe Gly Ser 965 970 975 tat tta cta ata ggg aaa gat aca tct ctg ctt gga aat ggc cag atg 3151 Tyr Leu Leu Ile Gly Lys Asp Thr Ser Leu Leu Gly Asn Gly Gln Met 980 985 990 995 ttt gga aac tgg aca ttt ggc act ttg gtc ttc aca gtc atg gtt att 3199 Phe Gly Asn Trp Thr Phe Gly Thr Leu Val Phe Thr Val Met Val Ile 1000 1005 1010 aca gtc aca gta aag atg gct ctg gaa act cat ttt tgg act tgg atc 3247 Thr Val Thr Val Lys Met Ala Leu Glu Thr His Phe Trp Thr Trp Ile 1015 1020 1025 aac cat ctc gtt acc tgg gga tct att ata ttt tat ttt gta ttt tcc 3295 Asn His Leu Val Thr Trp Gly Ser Ile Ile Phe Tyr Phe Val Phe Ser 1030 1035 1040 ttg ttt tat gga ggg att ctc tgg cca ttt ttg ggc tcc cag aat atg 3343 Leu Phe Tyr Gly Gly Ile Leu Trp Pro Phe Leu Gly Ser Gln Asn Met 1045 1050 1055 tat ttt gtg ttt att cag ctc ctg tca agt ggt tct gct tgg ttt gcc 3391 Tyr Phe Val Phe Ile Gln Leu Leu Ser Ser Gly Ser Ala Trp Phe Ala 1060 1065 1070 1075 ata atc ctc atg gtt gtt aca tgt cta ttt ctt gat atc ata aag aag 3439 Ile Ile Leu Met Val Val Thr Cys Leu Phe Leu Asp Ile Ile Lys Lys 1080 1085 1090 gtc ttt gac cga cac ctc cac cct aca agt act gaa aag gca cag ctt 3487 Val Phe Asp Arg His Leu His Pro Thr Ser Thr Glu Lys Ala Gln Leu 1095 1100 1105 act gaa aca aat gca ggt atc aag tgc ttg gac tcc atg tgc tgt ttc 3535 Thr Glu Thr Asn Ala Gly Ile Lys Cys Leu Asp Ser Met Cys Cys Phe 1110 1115 1120 ccg gaa gga gaa gca gcg tgt gca tct gtt gga aga atg ctg gaa cga 3583 Pro Glu Gly Glu Ala Ala Cys Ala Ser Val Gly Arg Met Leu Glu Arg 1125 1130 1135 gtt ata gga aga tgt agt cca acc cac atc agc agt tca tgg agt gca 3631 Val Ile Gly Arg Cys Ser Pro Thr His Ile Ser Ser Ser Trp Ser Ala 1140 1145 1150 1155 tcg gat cct ttc tat acc aac gac agg agc atc ttg act ctc tcc aca 3679 Ser Asp Pro Phe Tyr Thr Asn Asp Arg Ser Ile Leu Thr Leu Ser Thr 1160 1165 1170 atg gac tca tct act tgt taa aggggcagta gtactttgtg ggagccagtt 3730 Met Asp Ser Ser Thr Cys * 1175 cacctccttt cctaaaattc agtgtgatca ccctgttaat ggccacacta gctctgaaat 3790 taatttccaa aatctttgta gtagttcata cccactcaga gttataatgg caaacaaaca 3850 gaaagcatta gtacaagccc ctcccaacac ccttaatttg aatctgaaca tgttaaaatt 3910 tgagaataaa gagacatttt tcatctcttt gtctggtttg tcccttgtgc ttatgggact 3970 cctaatggca tttcagtctg ttgctgaggc cattatattt taatataaat gtagaaaaaa 4030 gagagaaatc ttagtaaaga gtatttttta gtattagctt gattattgac tcttctattt 4090 aaatctgctt ctgtaaatta tgctgaaagt ttgccttgag aactctattt ttttattaga 4150 gttatattta aagcttttca tgggaaaagt taatgtgaat actgaggaat tttggtccct 4210 cagtgacctg tgttgttaat tcattaatgc attctgagtt cacagagcaa attaggagaa 4270 tcatttccaa ccattattta ctgcagtatg gggagtaaat ttataccaat tcctctaact 4330 gtactgtaac acagcctgta aagttagcca tataaatgca agggtatatc atatatacaa 4390 atcaggaatc aggtccgttc accgaacttc aaattgatgt ttactaatat ttttgtgaca 4450 gagtataaag accctatagt gggtaaatta gatactatta gcatattatt aatttaatgt 4510 ctttatcatt ggatcttttg catgctttaa tctggttaac atatttaaat ttgctttttt 4570 tctctttacc tgaaggctct gtgtatagta tttcatgaca tcgttgtaca gtttaactat 4630 caataaaaag tttggacagt atttaaatat tgcaaatatg tttaattata caaatcagaa 4690 tagtatgggt aattaaatga atacaaaaag aagagcctct ttctgcagcc gacttagaca 4750 tgctcttccc tttctataag ctagatttta gaataaaggg tttcagttaa taatcttatt 4810 ttcaggttat gtcatctaac ttatagcaaa ctaccacaat acagtgagtt ctgccagtgt 4870 cccagtacaa ggcatatttc aggtgtggct gtggaatgta aaaatgctca acttgtatca 4930 ggtaatgtta gcaataaatt aaatgctaag aatgattaat cgggtacatg ttactgtaat 4990 taactcattg cacttcaaaa cctaacttcc atcctgaatt tatcaagtag ttcagtattg 5050 tcatttgttt ttgttttatt gaaaagtaat gttgtcttaa gatttagaag tgattattag 5110 cttgagaact attacccagc tctaagcaaa taatgattgt atacatatta agataatggt 5170 taaatgcggt tttaccaagt tttcccttga aaatgtaatt cctttatgga gatttattgt 5230 gcagccctaa gcttccttcc catttcatga atataaggct tctagaattg gactggcagg 5290 ggaaagaatg gtagagacag aaattaagac tttatccttg tttgcttgta aactattatt 5350 ttcttgctaa tgtaacattt gtctgttcca gtgatgtaag gatattaagt tattaagcta 5410 aatattaatt ttcaaaaata gtccttcttt aacttagata tttcatagct ggatttagga 5470 agatctgtta ttctggaagt actaaaaaga ataatacaac gtacaatgtc tgcattcact 5530 aattcatgtt ccagaagagg aaataatgaa gatatactca gtagagtact aggtgggagg 5590 atatggaaat ttgctcataa aatctcttat aaaacgtgca tataacaaaa tgacacccag 5650 taggcctgca ttacatttac atgaccgtgt ttatttgcca tcaaataaac tgagtactga 5710 caccagacaa agactccaaa gtcataaaat agcctatgac caactgcagc aagacaggag 5770 gtcagctcgc ctataatggt gcttaaagtg tgattgatgt aattttctgt actcaccatt 5830 tgaagttagt taaggagaac tttatttttt taaaaaaagt aaatggcaac cactagtgtg 5890 ctcatcctga actgttactc caaatccact ccgtttttaa agcaaaatta tcttgtgatt 5950 ttaagaaaag agttttctat ttatttaaga aagtaacaat gcagtctgca agctttcagt 6010 agttttctag tgctatattc atcctgtaaa actcttacta cgtaaccagt aatcacaagg 6070 aaagtgtccc ctttgcatat ttctttaaaa ttctttcttt ggaaagtatg atgttgataa 6130 ttaacttacc cttatctgcc aaaaccagag caaaatgcta aatacgttat tgctaatcag 6190 tggtctcaaa tcgatttgcc tccctttgcc tcgtctgagg gctgtaagcc tgaagatagt 6250 ggcaagcacc aagtcagttt ccaaaattgc ccctcagctg ctttaagtga ctcagcaccc 6310 tgcctcagct tcagcaggcg taggctcacc ctgggcggag caaagtatgg gccagggaga 6370 actacagcta cgaagacctg ctgtcgagtt gagaaaaggg gagaatttat ggtctgaatt 6430 ttctaactgt cctctttctt gggtctaaag ctcataatac acaaaggctt ccagacctga 6490 gccacaccca ggccctatcc tgaacaggag actaaacaga ggcaaatcaa ccctaggaaa 6550 tacttgcatt ctgccctacg gttagtacca ggactgaggt catttctact ggaaaagatt 6610 gtgagattga acttatctga tcgcttgaga ctcctaatag gcaggagtca aggccactag 6670 aaaattgaca gttaagagcc aaaagttttt aaaatatgct actctgaaaa atctcgtgaa 6730 ggctgtagga aaagggagaa tcttccatgt tggtgttttt cctgtaaaga tcagtttggg 6790 gtatgatata agcaggtatt aataaaaata acacaccaaa gagttacgta aaacatgttt 6850 tattaatttt ggtccccacg tacagacatt ttatttctat tttgaaatga gttatctatt 6910 ttcataaaag taaaacacta ttaaagtgct gttttatgtg aaataacttg aatgttgttc 6970 ctataaaaaa tagatcataa ctcatgatat gtttgtaatc atggtaattt agatttttat 7030 gaggaatgag tatctggaaa tattgtagca atacttggtt taaaattttg gacctgagac 7090 actgtggctg tctaatgtaa tcctttaaaa attctctgca ttgtcagtaa atgtagtata 7150 ttattgtaca gctactcata attttttaaa gtttatgaag ttatatttat caaataaaaa 7210 ctttcctata t 7221 <210> SEQ ID NO 20 <211> LENGTH: 1177 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 20 Met Trp Arg Trp Ile Arg Gln Gln Leu Gly Phe Asp Pro Pro His Gln 1 5 10 15 Ser Asp Thr Arg Thr Ile Tyr Val Ala His Arg Phe Pro Gln Asn Gly 20 25 30 Leu Tyr Thr Pro Gln Lys Phe Ile Asp Asn Arg Ile Ile Ser Ser Lys 35 40 45 Tyr Thr Val Trp Asn Phe Val Pro Lys Asn Leu Phe Glu Gln Phe Arg 50 55 60 Arg Val Ala Asn Phe Tyr Phe Leu Ile Ile Phe Leu Val Gln Leu Met 65 70 75 80 Ile Asp Thr Pro Thr Ser Pro Val Thr Ser Gly Leu Pro Leu Phe Phe 85 90 95 Val Ile Thr Val Thr Ala Ile Lys Gln Gly Tyr Glu Asp Trp Leu Arg 100 105 110 His Asn Ser Asp Asn Glu Val Asn Gly Ala Pro Val Tyr Val Val Arg 115 120 125 Ser Gly Gly Leu Val Lys Thr Arg Ser Lys Asn Ile Arg Val Gly Asp 130 135 140 Ile Val Arg Ile Ala Lys Asp Glu Ile Phe Pro Ala Asp Leu Val Leu 145 150 155 160 Leu Ser Ser Asp Arg Leu Asp Gly Ser Cys His Val Thr Thr Ala Ser 165 170 175 Leu Asp Gly Glu Thr Asn Leu Lys Thr His Val Ala Val Pro Glu Thr 180 185 190 Ala Leu Leu Gln Thr Val Ala Asn Leu Asp Thr Leu Val Ala Val Ile 195 200 205 Glu Cys Gln Gln Pro Glu Ala Asp Leu Tyr Arg Phe Met Gly Arg Met 210 215 220 Ile Ile Thr Gln Gln Met Glu Glu Ile Val Arg Pro Leu Gly Pro Glu 225 230 235 240 Ser Leu Leu Leu Arg Gly Ala Arg Leu Lys Asn Thr Lys Glu Ile Phe 245 250 255 Gly Val Ala Val Tyr Thr Gly Met Glu Thr Lys Met Ala Leu Asn Tyr 260 265 270 Lys Ser Lys Ser Gln Lys Arg Ser Ala Val Glu Lys Ser Met Asn Thr 275 280 285 Phe Leu Ile Ile Tyr Leu Val Ile Leu Ile Ser Glu Ala Val Ile Ser 290 295 300 Thr Ile Leu Lys Tyr Thr Trp Gln Ala Glu Glu Lys Trp Asp Glu Pro 305 310 315 320 Trp Tyr Asn Gln Lys Thr Glu His Gln Arg Asn Ser Ser Lys Ile Leu 325 330 335 Arg Phe Ile Ser Asp Phe Leu Ala Phe Leu Val Leu Tyr Asn Phe Ile 340 345 350 Ile Pro Ile Ser Leu Tyr Val Thr Val Glu Met Gln Lys Phe Leu Gly 355 360 365 Ser Phe Phe Ile Gly Trp Asp Leu Asp Leu Tyr His Glu Glu Ser Asp 370 375 380 Gln Lys Ala Gln Val Asn Thr Ser Asp Leu Asn Glu Glu Leu Gly Gln 385 390 395 400 Val Glu Tyr Val Phe Thr Asp Lys Thr Gly Thr Leu Thr Glu Asn Glu 405 410 415 Met Gln Phe Arg Glu Cys Ser Ile Asn Gly Met Lys Tyr Gln Glu Ile 420 425 430 Asn Gly Arg Leu Val Pro Glu Gly Pro Thr Pro Asp Ser Ser Glu Gly 435 440 445 Asn Leu Ser Tyr Leu Ser Ser Leu Ser His Leu Asn Asn Leu Ser His 450 455 460 Leu Thr Thr Ser Ser Ser Phe Arg Thr Ser Pro Glu Asn Glu Thr Glu 465 470 475 480 Leu Ile Lys Glu His Asp Leu Phe Phe Lys Ala Val Ser Leu Cys His 485 490 495 Thr Val Gln Ile Ser Asn Val Gln Thr Asp Cys Thr Gly Asp Gly Pro 500 505 510 Trp Gln Ser Asn Leu Ala Pro Ser Gln Leu Glu Tyr Tyr Ala Ser Ser 515 520 525 Pro Asp Glu Lys Ala Leu Val Glu Ala Ala Ala Arg Ile Gly Ile Val 530 535 540 Phe Ile Gly Asn Ser Glu Glu Thr Met Glu Val Lys Thr Leu Gly Lys 545 550 555 560 Leu Glu Arg Tyr Lys Leu Leu His Ile Leu Glu Phe Asp Ser Asp Arg 565 570 575 Arg Arg Met Ser Val Ile Val Gln Ala Pro Ser Gly Glu Lys Leu Leu 580 585 590 Phe Ala Lys Gly Ala Glu Ser Ser Ile Leu Pro Lys Cys Ile Gly Gly 595 600 605 Glu Ile Glu Lys Thr Arg Ile His Val Asp Glu Phe Ala Leu Lys Gly 610 615 620 Leu Arg Thr Leu Cys Ile Ala Tyr Arg Lys Phe Thr Ser Lys Glu Tyr 625 630 635 640 Glu Glu Ile Asp Lys Arg Ile Phe Glu Ala Arg Thr Ala Leu Gln Gln 645 650 655 Arg Glu Glu Lys Leu Ala Ala Val Phe Gln Phe Ile Glu Lys Asp Leu 660 665 670 Ile Leu Leu Gly Ala Thr Ala Val Glu Asp Arg Leu Gln Asp Lys Val 675 680 685 Arg Glu Thr Ile Glu Ala Leu Arg Met Ala Gly Ile Lys Val Trp Val 690 695 700 Leu Thr Gly Asp Lys His Glu Thr Ala Val Ser Val Ser Leu Ser Cys 705 710 715 720 Gly His Phe His Arg Thr Met Asn Ile Leu Glu Leu Ile Asn Gln Lys 725 730 735 Ser Asp Ser Glu Cys Ala Glu Gln Leu Arg Gln Leu Ala Arg Arg Ile 740 745 750 Thr Glu Asp His Val Ile Gln His Gly Leu Val Val Asp Gly Thr Ser 755 760 765 Leu Ser Leu Ala Leu Arg Glu His Glu Lys Leu Phe Met Glu Val Cys 770 775 780 Arg Asn Cys Ser Ala Val Leu Cys Cys Arg Met Ala Pro Leu Gln Lys 785 790 795 800 Ala Lys Val Ile Arg Leu Ile Lys Ile Ser Pro Glu Lys Pro Ile Thr 805 810 815 Leu Ala Val Gly Asp Gly Ala Asn Asp Val Ser Met Ile Gln Glu Ala 820 825 830 His Val Gly Ile Gly Ile Met Gly Lys Glu Gly Arg Gln Ala Ala Arg 835 840 845 Asn Ser Asp Tyr Ala Ile Ala Arg Phe Lys Phe Leu Ser Lys Leu Leu 850 855 860 Phe Val His Gly His Phe Tyr Tyr Ile Arg Ile Ala Thr Leu Val Gln 865 870 875 880 Tyr Phe Phe Tyr Lys Asn Val Cys Phe Ile Thr Pro Gln Phe Leu Tyr 885 890 895 Gln Phe Tyr Cys Leu Phe Ser Gln Gln Thr Leu Tyr Asp Ser Val Tyr 900 905 910 Leu Thr Leu Tyr Asn Ile Cys Phe Thr Ser Leu Pro Ile Leu Ile Tyr 915 920 925 Ser Leu Leu Glu Gln His Val Asp Pro His Val Leu Gln Asn Lys Pro 930 935 940 Thr Leu Tyr Arg Asp Ile Ser Lys Asn Arg Leu Leu Ser Ile Lys Thr 945 950 955 960 Phe Leu Tyr Trp Thr Ile Leu Gly Phe Ser His Ala Phe Ile Phe Phe 965 970 975 Phe Gly Ser Tyr Leu Leu Ile Gly Lys Asp Thr Ser Leu Leu Gly Asn 980 985 990 Gly Gln Met Phe Gly Asn Trp Thr Phe Gly Thr Leu Val Phe Thr Val 995 1000 1005 Met Val Ile Thr Val Thr Val Lys Met Ala Leu Glu Thr His Phe Trp 1010 1015 1020 Thr Trp Ile Asn His Leu Val Thr Trp Gly Ser Ile Ile Phe Tyr Phe 1025 1030 1035 1040 Val Phe Ser Leu Phe Tyr Gly Gly Ile Leu Trp Pro Phe Leu Gly Ser 1045 1050 1055 Gln Asn Met Tyr Phe Val Phe Ile Gln Leu Leu Ser Ser Gly Ser Ala 1060 1065 1070 Trp Phe Ala Ile Ile Leu Met Val Val Thr Cys Leu Phe Leu Asp Ile 1075 1080 1085 Ile Lys Lys Val Phe Asp Arg His Leu His Pro Thr Ser Thr Glu Lys 1090 1095 1100 Ala Gln Leu Thr Glu Thr Asn Ala Gly Ile Lys Cys Leu Asp Ser Met 1105 1110 1115 1120 Cys Cys Phe Pro Glu Gly Glu Ala Ala Cys Ala Ser Val Gly Arg Met 1125 1130 1135 Leu Glu Arg Val Ile Gly Arg Cys Ser Pro Thr His Ile Ser Ser Ser 1140 1145 1150 Trp Ser Ala Ser Asp Pro Phe Tyr Thr Asn Asp Arg Ser Ile Leu Thr 1155 1160 1165 Leu Ser Thr Met Asp Ser Ser Thr Cys 1170 1175 <210> SEQ ID NO 21 <211> LENGTH: 3534 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(3534) <400> SEQUENCE: 21 atg tgg cgc tgg atc cgg cag cag ctg ggt ttt gac cca cca cat cag 48 Met Trp Arg Trp Ile Arg Gln Gln Leu Gly Phe Asp Pro Pro His Gln 1 5 10 15 agt gac aca aga acc atc tac gta gcc cac agg ttt cct cag aat ggc 96 Ser Asp Thr Arg Thr Ile Tyr Val Ala His Arg Phe Pro Gln Asn Gly 20 25 30 ctt tac aca cct cag aaa ttt ata gat aac agg atc att tca tct aag 144 Leu Tyr Thr Pro Gln Lys Phe Ile Asp Asn Arg Ile Ile Ser Ser Lys 35 40 45 tac act gtg tgg aat ttt gtt cca aaa aat tta ttt gaa cag ttc aga 192 Tyr Thr Val Trp Asn Phe Val Pro Lys Asn Leu Phe Glu Gln Phe Arg 50 55 60 aga gtg gca aac ttt tat ttt ctt att ata ttt ttg gtt cag ctt atg 240 Arg Val Ala Asn Phe Tyr Phe Leu Ile Ile Phe Leu Val Gln Leu Met 65 70 75 80 att gat aca cct acc agt cca gtt acc agt gga ctt cca tta ttc ttt 288 Ile Asp Thr Pro Thr Ser Pro Val Thr Ser Gly Leu Pro Leu Phe Phe 85 90 95 gtg ata aca gta act gcc ata aag cag gga tat gaa gat tgg tta cgg 336 Val Ile Thr Val Thr Ala Ile Lys Gln Gly Tyr Glu Asp Trp Leu Arg 100 105 110 cat aac tca gat aat gaa gta aat gga gct cct gtt tat gtt gtt cga 384 His Asn Ser Asp Asn Glu Val Asn Gly Ala Pro Val Tyr Val Val Arg 115 120 125 agt ggt ggc ctt gta aaa act aga tca aaa aac att cgg gtg ggt gat 432 Ser Gly Gly Leu Val Lys Thr Arg Ser Lys Asn Ile Arg Val Gly Asp 130 135 140 att gtt cga ata gcc aaa gat gaa att ttt cct gca gac ttg gtg ctt 480 Ile Val Arg Ile Ala Lys Asp Glu Ile Phe Pro Ala Asp Leu Val Leu 145 150 155 160 ctg tcc tca gat cga ctg gat ggt tcc tgt cac gtt aca act gct agt 528 Leu Ser Ser Asp Arg Leu Asp Gly Ser Cys His Val Thr Thr Ala Ser 165 170 175 ttg gac gga gaa act aac ctg aag aca cat gtg gca gtt cca gaa aca 576 Leu Asp Gly Glu Thr Asn Leu Lys Thr His Val Ala Val Pro Glu Thr 180 185 190 gca tta tta caa aca gtt gcc aat ttg gac act cta gta gct gta ata 624 Ala Leu Leu Gln Thr Val Ala Asn Leu Asp Thr Leu Val Ala Val Ile 195 200 205 gaa tgc cag caa cca gaa gca gac tta tac aga ttc atg gga cga atg 672 Glu Cys Gln Gln Pro Glu Ala Asp Leu Tyr Arg Phe Met Gly Arg Met 210 215 220 atc ata acc caa caa atg gaa gaa att gta aga cct ctg ggg ccg gag 720 Ile Ile Thr Gln Gln Met Glu Glu Ile Val Arg Pro Leu Gly Pro Glu 225 230 235 240 agt ctc ctg ctt cgt gga gcc aga tta aaa aac aca aaa gaa att ttt 768 Ser Leu Leu Leu Arg Gly Ala Arg Leu Lys Asn Thr Lys Glu Ile Phe 245 250 255 ggt gtt gcg gta tac act gga atg gaa act aag atg gca tta aat tac 816 Gly Val Ala Val Tyr Thr Gly Met Glu Thr Lys Met Ala Leu Asn Tyr 260 265 270 aag agc aaa tca cag aaa cga tct gca gta gaa aag tca atg aat aca 864 Lys Ser Lys Ser Gln Lys Arg Ser Ala Val Glu Lys Ser Met Asn Thr 275 280 285 ttt ttg ata att tat cta gta att ctt ata tct gaa gct gtc atc agc 912 Phe Leu Ile Ile Tyr Leu Val Ile Leu Ile Ser Glu Ala Val Ile Ser 290 295 300 act atc ttg aag tat aca tgg caa gct gaa gaa aaa tgg gat gaa cct 960 Thr Ile Leu Lys Tyr Thr Trp Gln Ala Glu Glu Lys Trp Asp Glu Pro 305 310 315 320 tgg tat aac caa aaa aca gaa cat caa aga aat agc agt aag att ctg 1008 Trp Tyr Asn Gln Lys Thr Glu His Gln Arg Asn Ser Ser Lys Ile Leu 325 330 335 aga ttt att tca gac ttc ctt gct ttt ttg gtt ctc tac aat ttc atc 1056 Arg Phe Ile Ser Asp Phe Leu Ala Phe Leu Val Leu Tyr Asn Phe Ile 340 345 350 att cca att tca tta tat gtg aca gtc gaa atg cag aaa ttt ctt gga 1104 Ile Pro Ile Ser Leu Tyr Val Thr Val Glu Met Gln Lys Phe Leu Gly 355 360 365 tca ttt ttt att ggc tgg gat ctt gat ctg tat cat gaa gaa tca gat 1152 Ser Phe Phe Ile Gly Trp Asp Leu Asp Leu Tyr His Glu Glu Ser Asp 370 375 380 cag aaa gct caa gtc aat act tcc gat ctg aat gaa gag ctt gga cag 1200 Gln Lys Ala Gln Val Asn Thr Ser Asp Leu Asn Glu Glu Leu Gly Gln 385 390 395 400 gta gag tac gtg ttt aca gat aaa act ggt aca ctg aca gaa aat gag 1248 Val Glu Tyr Val Phe Thr Asp Lys Thr Gly Thr Leu Thr Glu Asn Glu 405 410 415 atg cag ttt cgg gaa tgt tca att aat ggc atg aaa tac caa gaa att 1296 Met Gln Phe Arg Glu Cys Ser Ile Asn Gly Met Lys Tyr Gln Glu Ile 420 425 430 aat ggt aga ctt gta ccc gaa gga cca aca cca gac tct tca gaa gga 1344 Asn Gly Arg Leu Val Pro Glu Gly Pro Thr Pro Asp Ser Ser Glu Gly 435 440 445 aac tta tct tat ctt agt agt tta tcc cat ctt aac aac tta tcc cat 1392 Asn Leu Ser Tyr Leu Ser Ser Leu Ser His Leu Asn Asn Leu Ser His 450 455 460 ctt aca acc agt tcc tct ttc aga acc agt cct gaa aat gaa act gaa 1440 Leu Thr Thr Ser Ser Ser Phe Arg Thr Ser Pro Glu Asn Glu Thr Glu 465 470 475 480 cta att aaa gaa cat gat ctc ttc ttt aaa gca gtc agt ctc tgt cac 1488 Leu Ile Lys Glu His Asp Leu Phe Phe Lys Ala Val Ser Leu Cys His 485 490 495 act gta cag att agc aat gtt caa act gac tgc act ggt gat ggt ccc 1536 Thr Val Gln Ile Ser Asn Val Gln Thr Asp Cys Thr Gly Asp Gly Pro 500 505 510 tgg caa tcc aac ctg gca cca tcg cag ttg gag tac tat gca tct tca 1584 Trp Gln Ser Asn Leu Ala Pro Ser Gln Leu Glu Tyr Tyr Ala Ser Ser 515 520 525 cca gat gaa aag gct cta gta gaa gct gct gca agg att ggt att gtg 1632 Pro Asp Glu Lys Ala Leu Val Glu Ala Ala Ala Arg Ile Gly Ile Val 530 535 540 ttt att ggc aat tct gaa gaa act atg gag gtt aaa act ctt gga aaa 1680 Phe Ile Gly Asn Ser Glu Glu Thr Met Glu Val Lys Thr Leu Gly Lys 545 550 555 560 ctg gaa cgg tac aaa ctg ctt cat att ctg gaa ttt gat tca gat cgt 1728 Leu Glu Arg Tyr Lys Leu Leu His Ile Leu Glu Phe Asp Ser Asp Arg 565 570 575 agg aga atg agt gta att gtt cag gca cct tca ggt gag aag tta tta 1776 Arg Arg Met Ser Val Ile Val Gln Ala Pro Ser Gly Glu Lys Leu Leu 580 585 590 ttt gct aaa gga gct gag tca tca att ctc cct aaa tgt ata ggt gga 1824 Phe Ala Lys Gly Ala Glu Ser Ser Ile Leu Pro Lys Cys Ile Gly Gly 595 600 605 gaa ata gaa aaa acc aga att cat gta gat gaa ttt gct ttg aaa ggg 1872 Glu Ile Glu Lys Thr Arg Ile His Val Asp Glu Phe Ala Leu Lys Gly 610 615 620 cta aga act ctg tgt ata gca tat aga aaa ttt aca tca aaa gag tat 1920 Leu Arg Thr Leu Cys Ile Ala Tyr Arg Lys Phe Thr Ser Lys Glu Tyr 625 630 635 640 gag gaa ata gat aaa cgc ata ttt gaa gcc agg act gcc ttg cag cag 1968 Glu Glu Ile Asp Lys Arg Ile Phe Glu Ala Arg Thr Ala Leu Gln Gln 645 650 655 cgg gaa gag aaa ttg gca gct gtt ttc cag ttc ata gag aaa gac ctg 2016 Arg Glu Glu Lys Leu Ala Ala Val Phe Gln Phe Ile Glu Lys Asp Leu 660 665 670 ata tta ctt gga gcc aca gca gta gaa gac aga cta caa gat aaa gtt 2064 Ile Leu Leu Gly Ala Thr Ala Val Glu Asp Arg Leu Gln Asp Lys Val 675 680 685 cga gaa act att gaa gca ttg aga atg gct ggt atc aaa gta tgg gta 2112 Arg Glu Thr Ile Glu Ala Leu Arg Met Ala Gly Ile Lys Val Trp Val 690 695 700 ctt act ggg gat aaa cat gaa aca gct gtt agt gtg agt tta tca tgt 2160 Leu Thr Gly Asp Lys His Glu Thr Ala Val Ser Val Ser Leu Ser Cys 705 710 715 720 ggc cat ttt cat aga acc atg aac atc ctt gaa ctt ata aac cag aaa 2208 Gly His Phe His Arg Thr Met Asn Ile Leu Glu Leu Ile Asn Gln Lys 725 730 735 tca gac agc gag tgt gct gaa caa ttg agg cag ctt gcc aga aga att 2256 Ser Asp Ser Glu Cys Ala Glu Gln Leu Arg Gln Leu Ala Arg Arg Ile 740 745 750 aca gag gat cat gtg att cag cat ggg ctg gta gtg gat ggg acc agc 2304 Thr Glu Asp His Val Ile Gln His Gly Leu Val Val Asp Gly Thr Ser 755 760 765 cta tct ctt gca ctc agg gag cat gaa aaa cta ttt atg gaa gtt tgc 2352 Leu Ser Leu Ala Leu Arg Glu His Glu Lys Leu Phe Met Glu Val Cys 770 775 780 aga aat tgt tca gct gta tta tgc tgt cgt atg gct cca ctg cag aaa 2400 Arg Asn Cys Ser Ala Val Leu Cys Cys Arg Met Ala Pro Leu Gln Lys 785 790 795 800 gca aaa gta ata aga cta ata aaa ata tca cct gag aaa cct ata aca 2448 Ala Lys Val Ile Arg Leu Ile Lys Ile Ser Pro Glu Lys Pro Ile Thr 805 810 815 ttg gct gtt ggt gat ggt gct aat gac gta agc atg ata caa gaa gcc 2496 Leu Ala Val Gly Asp Gly Ala Asn Asp Val Ser Met Ile Gln Glu Ala 820 825 830 cat gtt ggc ata gga atc atg ggt aaa gaa gga aga cag gct gca aga 2544 His Val Gly Ile Gly Ile Met Gly Lys Glu Gly Arg Gln Ala Ala Arg 835 840 845 aac agt gac tat gca ata gcc aga ttt aag ttc ctc tcc aaa ttg ctt 2592 Asn Ser Asp Tyr Ala Ile Ala Arg Phe Lys Phe Leu Ser Lys Leu Leu 850 855 860 ttt gtt cat ggt cat ttt tat tat att aga ata gct acc ctt gta cag 2640 Phe Val His Gly His Phe Tyr Tyr Ile Arg Ile Ala Thr Leu Val Gln 865 870 875 880 tat ttt ttt tat aag aat gtg tgc ttt atc aca ccc cag ttt tta tat 2688 Tyr Phe Phe Tyr Lys Asn Val Cys Phe Ile Thr Pro Gln Phe Leu Tyr 885 890 895 cag ttc tac tgt ttg ttt tct cag caa aca ttg tat gac agc gtg tac 2736 Gln Phe Tyr Cys Leu Phe Ser Gln Gln Thr Leu Tyr Asp Ser Val Tyr 900 905 910 ctg act tta tac aat att tgt ttt act tcc cta cct att ctg ata tat 2784 Leu Thr Leu Tyr Asn Ile Cys Phe Thr Ser Leu Pro Ile Leu Ile Tyr 915 920 925 agt ctt ttg gaa cag cat gta gac cct cat gtg tta caa aat aag ccc 2832 Ser Leu Leu Glu Gln His Val Asp Pro His Val Leu Gln Asn Lys Pro 930 935 940 acc ctt tat cga gac att agt aaa aac cgc ctc tta agt att aaa aca 2880 Thr Leu Tyr Arg Asp Ile Ser Lys Asn Arg Leu Leu Ser Ile Lys Thr 945 950 955 960 ttt ctt tat tgg acc atc ctg ggc ttc agt cat gcc ttt att ttc ttt 2928 Phe Leu Tyr Trp Thr Ile Leu Gly Phe Ser His Ala Phe Ile Phe Phe 965 970 975 ttt gga tcc tat tta cta ata ggg aaa gat aca tct ctg ctt gga aat 2976 Phe Gly Ser Tyr Leu Leu Ile Gly Lys Asp Thr Ser Leu Leu Gly Asn 980 985 990 ggc cag atg ttt gga aac tgg aca ttt ggc act ttg gtc ttc aca gtc 3024 Gly Gln Met Phe Gly Asn Trp Thr Phe Gly Thr Leu Val Phe Thr Val 995 1000 1005 atg gtt att aca gtc aca gta aag atg gct ctg gaa act cat ttt tgg 3072 Met Val Ile Thr Val Thr Val Lys Met Ala Leu Glu Thr His Phe Trp 1010 1015 1020 act tgg atc aac cat ctc gtt acc tgg gga tct att ata ttt tat ttt 3120 Thr Trp Ile Asn His Leu Val Thr Trp Gly Ser Ile Ile Phe Tyr Phe 1025 1030 1035 1040 gta ttt tcc ttg ttt tat gga ggg att ctc tgg cca ttt ttg ggc tcc 3168 Val Phe Ser Leu Phe Tyr Gly Gly Ile Leu Trp Pro Phe Leu Gly Ser 1045 1050 1055 cag aat atg tat ttt gtg ttt att cag ctc ctg tca agt ggt tct gct 3216 Gln Asn Met Tyr Phe Val Phe Ile Gln Leu Leu Ser Ser Gly Ser Ala 1060 1065 1070 tgg ttt gcc ata atc ctc atg gtt gtt aca tgt cta ttt ctt gat atc 3264 Trp Phe Ala Ile Ile Leu Met Val Val Thr Cys Leu Phe Leu Asp Ile 1075 1080 1085 ata aag aag gtc ttt gac cga cac ctc cac cct aca agt act gaa aag 3312 Ile Lys Lys Val Phe Asp Arg His Leu His Pro Thr Ser Thr Glu Lys 1090 1095 1100 gca cag ctt act gaa aca aat gca ggt atc aag tgc ttg gac tcc atg 3360 Ala Gln Leu Thr Glu Thr Asn Ala Gly Ile Lys Cys Leu Asp Ser Met 1105 1110 1115 1120 tgc tgt ttc ccg gaa gga gaa gca gcg tgt gca tct gtt gga aga atg 3408 Cys Cys Phe Pro Glu Gly Glu Ala Ala Cys Ala Ser Val Gly Arg Met 1125 1130 1135 ctg gaa cga gtt ata gga aga tgt agt cca acc cac atc agc agt tca 3456 Leu Glu Arg Val Ile Gly Arg Cys Ser Pro Thr His Ile Ser Ser Ser 1140 1145 1150 tgg agt gca tcg gat cct ttc tat acc aac gac agg agc atc ttg act 3504 Trp Ser Ala Ser Asp Pro Phe Tyr Thr Asn Asp Arg Ser Ile Leu Thr 1155 1160 1165 ctc tcc aca atg gac tca tct act tgt taa 3534 Leu Ser Thr Met Asp Ser Ser Thr Cys * 1170 1175 <210> SEQ ID NO 22 <211> LENGTH: 4198 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (156)...(3410) <400> SEQUENCE: 22 ggagtcgacc cacgcgtccg cattgagaca atgcctccac aaatacttga tgcaaaattc 60 agtaagacag cacttgttga atcaccatta tagtttctga caaattgttc tcaaaaaggt 120 accagctgga ggatgagtct gcgcatttgg atgaa atg cca cta atg atg tct 173 Met Pro Leu Met Met Ser 1 5 gaa gaa ggc ttt gag aat gag gaa agt gat tac cac acc tta cca cga 221 Glu Glu Gly Phe Glu Asn Glu Glu Ser Asp Tyr His Thr Leu Pro Arg 10 15 20 gcc agg ata atg caa agg aaa aga gga ctg gag tgg ttt gtc tgt gat 269 Ala Arg Ile Met Gln Arg Lys Arg Gly Leu Glu Trp Phe Val Cys Asp 25 30 35 ggc tgg aag ttc ctc tgt acc agt tgc tgt ggt tgg ctg ata aat att 317 Gly Trp Lys Phe Leu Cys Thr Ser Cys Cys Gly Trp Leu Ile Asn Ile 40 45 50 tgt cga aga aag aaa gag ctg aaa gct cgc aca gta tgg ctt gga tgt 365 Cys Arg Arg Lys Lys Glu Leu Lys Ala Arg Thr Val Trp Leu Gly Cys 55 60 65 70 cct gaa aag tgt gaa gaa aaa cat ccc agg aat tct ata aaa aat caa 413 Pro Glu Lys Cys Glu Glu Lys His Pro Arg Asn Ser Ile Lys Asn Gln 75 80 85 aaa tac aat gtg ttt acc ttt ata cct ggg gtt ttg tat gaa caa ttc 461 Lys Tyr Asn Val Phe Thr Phe Ile Pro Gly Val Leu Tyr Glu Gln Phe 90 95 100 aag ttt ttc ttg aat ctc tat ttt cta gtg ata tcc tgc tca cag ttt 509 Lys Phe Phe Leu Asn Leu Tyr Phe Leu Val Ile Ser Cys Ser Gln Phe 105 110 115 gta cca gca ttg aaa ata ggc tat ctc tac acc tac tgg gct cct ctg 557 Val Pro Ala Leu Lys Ile Gly Tyr Leu Tyr Thr Tyr Trp Ala Pro Leu 120 125 130 gga ttt gtc ttg gct gtt act atg aca cgg gaa gca att gat gaa ttt 605 Gly Phe Val Leu Ala Val Thr Met Thr Arg Glu Ala Ile Asp Glu Phe 135 140 145 150 cgg cgt ttt cag cgt gac aag gaa gtg aat tca caa cta tat agc aag 653 Arg Arg Phe Gln Arg Asp Lys Glu Val Asn Ser Gln Leu Tyr Ser Lys 155 160 165 ctt aca gta aga ggt aaa gtg caa gtt aag agt tca gac ata caa gtt 701 Leu Thr Val Arg Gly Lys Val Gln Val Lys Ser Ser Asp Ile Gln Val 170 175 180 gga gac ctc atc ata gtg gaa aag aat caa aga att cca tcg gac atg 749 Gly Asp Leu Ile Ile Val Glu Lys Asn Gln Arg Ile Pro Ser Asp Met 185 190 195 gtg ttt ctt agg act tca gaa aaa gca ggt tcg tgt ttt att cga act 797 Val Phe Leu Arg Thr Ser Glu Lys Ala Gly Ser Cys Phe Ile Arg Thr 200 205 210 gat caa cta gat ggt gaa act gac tgg aag ctg aag gtg gca gtg agc 845 Asp Gln Leu Asp Gly Glu Thr Asp Trp Lys Leu Lys Val Ala Val Ser 215 220 225 230 tgc acg caa cag ctg ccg gct ctg ggg gac ctt ttt tct atc agt gct 893 Cys Thr Gln Gln Leu Pro Ala Leu Gly Asp Leu Phe Ser Ile Ser Ala 235 240 245 tat gtt tat gct cag aaa cca caa atg gac att cac agt ttc gaa ggc 941 Tyr Val Tyr Ala Gln Lys Pro Gln Met Asp Ile His Ser Phe Glu Gly 250 255 260 aca ttt acc agg gaa gac agt gac ccg ccc att cat gaa agt ctc agc 989 Thr Phe Thr Arg Glu Asp Ser Asp Pro Pro Ile His Glu Ser Leu Ser 265 270 275 ata gaa aat aca ttg tgg gca agc acc att gtt gca tca ggt act gta 1037 Ile Glu Asn Thr Leu Trp Ala Ser Thr Ile Val Ala Ser Gly Thr Val 280 285 290 ata ggt gtt gtc att tat acc gga aaa gag act cga agt gta atg aac 1085 Ile Gly Val Val Ile Tyr Thr Gly Lys Glu Thr Arg Ser Val Met Asn 295 300 305 310 aca tcc aat cca aaa aat aag gtt ggt ttg ttg gac ctt gaa ctc aat 1133 Thr Ser Asn Pro Lys Asn Lys Val Gly Leu Leu Asp Leu Glu Leu Asn 315 320 325 cgg ctg acg aaa gcg cta ttt ttg gct tta gtt gct ctt tcc att gtt 1181 Arg Leu Thr Lys Ala Leu Phe Leu Ala Leu Val Ala Leu Ser Ile Val 330 335 340 atg gta acc tta caa gga ttt gtg ggt cca tgg tac cgc aat ctt ttt 1229 Met Val Thr Leu Gln Gly Phe Val Gly Pro Trp Tyr Arg Asn Leu Phe 345 350 355 cgg ttc ctt ctc ctc ttt tct tac atc att ccc ata agt ttg cgt gtg 1277 Arg Phe Leu Leu Leu Phe Ser Tyr Ile Ile Pro Ile Ser Leu Arg Val 360 365 370 aac ttg gac atg ggc aaa gcg gtg tat gga tgg atg atg atg aaa gat 1325 Asn Leu Asp Met Gly Lys Ala Val Tyr Gly Trp Met Met Met Lys Asp 375 380 385 390 gag aac atc cct ggc acg gtc gtt cgg acc agc act atc cca gag gaa 1373 Glu Asn Ile Pro Gly Thr Val Val Arg Thr Ser Thr Ile Pro Glu Glu 395 400 405 ctt ggg cgc ctg gtg tat tta ttg aca gac aaa aca gga acc ctc acc 1421 Leu Gly Arg Leu Val Tyr Leu Leu Thr Asp Lys Thr Gly Thr Leu Thr 410 415 420 cag aat gaa atg ata ttt aag cgg ctg cac ctg ggc acc gtg tcc tat 1469 Gln Asn Glu Met Ile Phe Lys Arg Leu His Leu Gly Thr Val Ser Tyr 425 430 435 ggc gcc gac acg atg gat gag atc cag agc cat gtc agg gac tcc tac 1517 Gly Ala Asp Thr Met Asp Glu Ile Gln Ser His Val Arg Asp Ser Tyr 440 445 450 tca cag atg cag tct caa gct ggt gga aac aat act ggt tca act cca 1565 Ser Gln Met Gln Ser Gln Ala Gly Gly Asn Asn Thr Gly Ser Thr Pro 455 460 465 470 cta aga aaa gcc caa tct tca gct ccc aaa gtt agg aaa agt gtc agt 1613 Leu Arg Lys Ala Gln Ser Ser Ala Pro Lys Val Arg Lys Ser Val Ser 475 480 485 agt cga atc cat gaa gcc gtg aaa gcc atc gtg ctg tgt cac aac gtg 1661 Ser Arg Ile His Glu Ala Val Lys Ala Ile Val Leu Cys His Asn Val 490 495 500 acc ccc gtg tat gag tct cgg gcc ggc gtt act gag gag act gag ttc 1709 Thr Pro Val Tyr Glu Ser Arg Ala Gly Val Thr Glu Glu Thr Glu Phe 505 510 515 gca gag gct gac caa gac ttc agt gat gag aat cgc acc tac cag gct 1757 Ala Glu Ala Asp Gln Asp Phe Ser Asp Glu Asn Arg Thr Tyr Gln Ala 520 525 530 tcc agc ccg gat gag gtc gct ctg gtg cag tgg aca gag agt gtg ggc 1805 Ser Ser Pro Asp Glu Val Ala Leu Val Gln Trp Thr Glu Ser Val Gly 535 540 545 550 ctc acg ctg gtc agc agg gac ctc acc tcc atg cag ctg aag acc ccc 1853 Leu Thr Leu Val Ser Arg Asp Leu Thr Ser Met Gln Leu Lys Thr Pro 555 560 565 agt ggc cag gtc ctc agc ttc tgc att ctg cag ctg ttt ccc ttc acc 1901 Ser Gly Gln Val Leu Ser Phe Cys Ile Leu Gln Leu Phe Pro Phe Thr 570 575 580 tcc gag agc aag cgg atg ggc gtc atc gtc agg gat gaa tcc acg gca 1949 Ser Glu Ser Lys Arg Met Gly Val Ile Val Arg Asp Glu Ser Thr Ala 585 590 595 gaa atc aca ttc tac atg aag ggc gct gac gtg gcc atg tct cct atc 1997 Glu Ile Thr Phe Tyr Met Lys Gly Ala Asp Val Ala Met Ser Pro Ile 600 605 610 gtg cag tat aat gac tgg ctg gaa gag gag tgc gga aac atg gct cgc 2045 Val Gln Tyr Asn Asp Trp Leu Glu Glu Glu Cys Gly Asn Met Ala Arg 615 620 625 630 gaa gga ctg cgg acc ctc gtg gtt gca aag aag gcg ttg aca gag gag 2093 Glu Gly Leu Arg Thr Leu Val Val Ala Lys Lys Ala Leu Thr Glu Glu 635 640 645 cag tac cag gac ttt gag agc cga tac act caa gcc aag ctg agc atg 2141 Gln Tyr Gln Asp Phe Glu Ser Arg Tyr Thr Gln Ala Lys Leu Ser Met 650 655 660 cac gac agg tcc ctc aag gtg gcc gcg gta gtc gag agc ctg gag agg 2189 His Asp Arg Ser Leu Lys Val Ala Ala Val Val Glu Ser Leu Glu Arg 665 670 675 gag atg gaa ctg ctg tgc ctc acc ggc gtg gag gac cag ctg cag gca 2237 Glu Met Glu Leu Leu Cys Leu Thr Gly Val Glu Asp Gln Leu Gln Ala 680 685 690 gac gtg cgg ccc acg ctg gag atg ctg cgc aac gcc ggg atc aag ata 2285 Asp Val Arg Pro Thr Leu Glu Met Leu Arg Asn Ala Gly Ile Lys Ile 695 700 705 710 tgg atg cta aca ggc gat aaa ctc gag aca gct acc tgc att gcc aaa 2333 Trp Met Leu Thr Gly Asp Lys Leu Glu Thr Ala Thr Cys Ile Ala Lys 715 720 725 agt tca cat ctc gtg tct aga aca caa gat att cat att ttc aga cag 2381 Ser Ser His Leu Val Ser Arg Thr Gln Asp Ile His Ile Phe Arg Gln 730 735 740 gta acc agt cgg gga gag gca cat ttg gag ctg aat gca ttt cga agg 2429 Val Thr Ser Arg Gly Glu Ala His Leu Glu Leu Asn Ala Phe Arg Arg 745 750 755 aag cat gat tgt gca cta gtc ata tct ggg gac tct ctg gag gtt tgt 2477 Lys His Asp Cys Ala Leu Val Ile Ser Gly Asp Ser Leu Glu Val Cys 760 765 770 cta aag tac tac gag cat gaa ttt gtg gag ctg gcc tgc cag tgc cct 2525 Leu Lys Tyr Tyr Glu His Glu Phe Val Glu Leu Ala Cys Gln Cys Pro 775 780 785 790 gcc gtg gtt tgc tgc cgc tgc tca ccc acc cag aag gcc cgc att gtg 2573 Ala Val Val Cys Cys Arg Cys Ser Pro Thr Gln Lys Ala Arg Ile Val 795 800 805 aca ctg ctg cag cag cac aca ggg aga cgc acc tgc gcc atc ggt gat 2621 Thr Leu Leu Gln Gln His Thr Gly Arg Arg Thr Cys Ala Ile Gly Asp 810 815 820 gga gga aat gat gtc agc atg att cag gca gca gac tgt ggg att ggg 2669 Gly Gly Asn Asp Val Ser Met Ile Gln Ala Ala Asp Cys Gly Ile Gly 825 830 835 att gag gga aag gag ggt aaa cag gcc tcg ctg gcg gcc gac ttc tcc 2717 Ile Glu Gly Lys Glu Gly Lys Gln Ala Ser Leu Ala Ala Asp Phe Ser 840 845 850 atc acg cag ttc cgg cac ata ggc agg ctg ctc atg gtg cac ggg cgg 2765 Ile Thr Gln Phe Arg His Ile Gly Arg Leu Leu Met Val His Gly Arg 855 860 865 870 aac agc tac aag agg tcg gcg gca ctc ggc cag ttc gtc atg cac agg 2813 Asn Ser Tyr Lys Arg Ser Ala Ala Leu Gly Gln Phe Val Met His Arg 875 880 885 ggc ctt atc atc tcc acc atg cag gct gtg ttt tcc tca gtc ttc tac 2861 Gly Leu Ile Ile Ser Thr Met Gln Ala Val Phe Ser Ser Val Phe Tyr 890 895 900 ttc gca tcc gtc cct ttg tat cag ggc ttc ctc atg gtg ggg tat gcc 2909 Phe Ala Ser Val Pro Leu Tyr Gln Gly Phe Leu Met Val Gly Tyr Ala 905 910 915 acc ata tac acc atg ttc cca gtg ttc tcc tta gtg ctg gac cag gac 2957 Thr Ile Tyr Thr Met Phe Pro Val Phe Ser Leu Val Leu Asp Gln Asp 920 925 930 gtg aag cca gag atg gcg atg ctc tac ccg gag ctg tac aag gac ctc 3005 Val Lys Pro Glu Met Ala Met Leu Tyr Pro Glu Leu Tyr Lys Asp Leu 935 940 945 950 acc aag gga aga tcc ttg tcc ttc aaa acc ttc ctc atc tgg gtt tta 3053 Thr Lys Gly Arg Ser Leu Ser Phe Lys Thr Phe Leu Ile Trp Val Leu 955 960 965 ata agt att tac caa ggc ggc atc ctc atg tat ggg gcc ctg gtg ctc 3101 Ile Ser Ile Tyr Gln Gly Gly Ile Leu Met Tyr Gly Ala Leu Val Leu 970 975 980 ttc gag tct gag ttc gtc cac gtg gtg gcc atc tcc ttc acc gca ctg 3149 Phe Glu Ser Glu Phe Val His Val Val Ala Ile Ser Phe Thr Ala Leu 985 990 995 atc ctg acc gag ctg ctg atg gtg gcg ctg acc gtc cgc acg tgg cac 3197 Ile Leu Thr Glu Leu Leu Met Val Ala Leu Thr Val Arg Thr Trp His 1000 1005 1010 tgg ctg atg gtg gtg gcc gag ttc ctc agc tta ggc tgc tac gtg tcc 3245 Trp Leu Met Val Val Ala Glu Phe Leu Ser Leu Gly Cys Tyr Val Ser 1015 1020 1025 1030 tca ctc gct ttt ctc aat gaa tat ttt gat gtt gcc ttt atc acc acc 3293 Ser Leu Ala Phe Leu Asn Glu Tyr Phe Asp Val Ala Phe Ile Thr Thr 1035 1040 1045 gtg acc ttc ctg tgg aaa gtg tcg gcg atc acc gtg gtc agc tgc ctc 3341 Val Thr Phe Leu Trp Lys Val Ser Ala Ile Thr Val Val Ser Cys Leu 1050 1055 1060 ccg ctg tat gtc ctc aag tac ctg agg cgc aag tct tct cct ccc agc 3389 Pro Leu Tyr Val Leu Lys Tyr Leu Arg Arg Lys Ser Ser Pro Pro Ser 1065 1070 1075 tac tgc aag ctg gcc tcc taa ggggctgtgc acccccagcg ggctggcccc 3440 Tyr Cys Lys Leu Ala Ser * 1080 agcaccttct gcccttccca gcaccttgtg cccttgccag tgaacgcagg gtttgccatt 3500 gctaccaagc aagcaccaca agaaagggag ggtacgccag gcgagcccag ggcacagatg 3560 ctgagacagc ctctccttct cagtgcaggg acgtcacccc tgccaggcaa gcccagggca 3620 cagatgccag gatggcttct ccctctcagt gcgaggcttc acccctgcca ggcaagccca 3680 gggcatagat gctgagacag cctctccctc tcagtgcagg gacgtcaccc ctgccaggca 3740 agcccagggc acagaggccg ggacggcctc tccctctcag tgtgaggctt cacccatgct 3800 aggcaagccc agggcacaga tgccgggatg gcccctccct ctcagtgcgg gaacgtcacc 3860 cctgccaggc aagcccaggg cacagatgct gcgatggcct cttcctctta agtgtggggc 3920 ctcacccctg cttttctttc tttttttgta ttgtcaaaat tgtatttcca tattgaagca 3980 gcttgagttt ctactgaaaa tgagcccgaa ttatttcact attactgtaa agggttcatc 4040 ttactctggc attctgagaa ttagactgaa agtttaattt ctgcagttcc ctcatattca 4100 gattctttct ttgatgttat aacacaaagt cattcctact caaatgtaat aaaattgagg 4160 ctccacggag aaaaaaaaaa aaaaaaaaaa aaaaaaaa 4198 <210> SEQ ID NO 23 <211> LENGTH: 1084 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 23 Met Pro Leu Met Met Ser Glu Glu Gly Phe Glu Asn Glu Glu Ser Asp 1 5 10 15 Tyr His Thr Leu Pro Arg Ala Arg Ile Met Gln Arg Lys Arg Gly Leu 20 25 30 Glu Trp Phe Val Cys Asp Gly Trp Lys Phe Leu Cys Thr Ser Cys Cys 35 40 45 Gly Trp Leu Ile Asn Ile Cys Arg Arg Lys Lys Glu Leu Lys Ala Arg 50 55 60 Thr Val Trp Leu Gly Cys Pro Glu Lys Cys Glu Glu Lys His Pro Arg 65 70 75 80 Asn Ser Ile Lys Asn Gln Lys Tyr Asn Val Phe Thr Phe Ile Pro Gly 85 90 95 Val Leu Tyr Glu Gln Phe Lys Phe Phe Leu Asn Leu Tyr Phe Leu Val 100 105 110 Ile Ser Cys Ser Gln Phe Val Pro Ala Leu Lys Ile Gly Tyr Leu Tyr 115 120 125 Thr Tyr Trp Ala Pro Leu Gly Phe Val Leu Ala Val Thr Met Thr Arg 130 135 140 Glu Ala Ile Asp Glu Phe Arg Arg Phe Gln Arg Asp Lys Glu Val Asn 145 150 155 160 Ser Gln Leu Tyr Ser Lys Leu Thr Val Arg Gly Lys Val Gln Val Lys 165 170 175 Ser Ser Asp Ile Gln Val Gly Asp Leu Ile Ile Val Glu Lys Asn Gln 180 185 190 Arg Ile Pro Ser Asp Met Val Phe Leu Arg Thr Ser Glu Lys Ala Gly 195 200 205 Ser Cys Phe Ile Arg Thr Asp Gln Leu Asp Gly Glu Thr Asp Trp Lys 210 215 220 Leu Lys Val Ala Val Ser Cys Thr Gln Gln Leu Pro Ala Leu Gly Asp 225 230 235 240 Leu Phe Ser Ile Ser Ala Tyr Val Tyr Ala Gln Lys Pro Gln Met Asp 245 250 255 Ile His Ser Phe Glu Gly Thr Phe Thr Arg Glu Asp Ser Asp Pro Pro 260 265 270 Ile His Glu Ser Leu Ser Ile Glu Asn Thr Leu Trp Ala Ser Thr Ile 275 280 285 Val Ala Ser Gly Thr Val Ile Gly Val Val Ile Tyr Thr Gly Lys Glu 290 295 300 Thr Arg Ser Val Met Asn Thr Ser Asn Pro Lys Asn Lys Val Gly Leu 305 310 315 320 Leu Asp Leu Glu Leu Asn Arg Leu Thr Lys Ala Leu Phe Leu Ala Leu 325 330 335 Val Ala Leu Ser Ile Val Met Val Thr Leu Gln Gly Phe Val Gly Pro 340 345 350 Trp Tyr Arg Asn Leu Phe Arg Phe Leu Leu Leu Phe Ser Tyr Ile Ile 355 360 365 Pro Ile Ser Leu Arg Val Asn Leu Asp Met Gly Lys Ala Val Tyr Gly 370 375 380 Trp Met Met Met Lys Asp Glu Asn Ile Pro Gly Thr Val Val Arg Thr 385 390 395 400 Ser Thr Ile Pro Glu Glu Leu Gly Arg Leu Val Tyr Leu Leu Thr Asp 405 410 415 Lys Thr Gly Thr Leu Thr Gln Asn Glu Met Ile Phe Lys Arg Leu His 420 425 430 Leu Gly Thr Val Ser Tyr Gly Ala Asp Thr Met Asp Glu Ile Gln Ser 435 440 445 His Val Arg Asp Ser Tyr Ser Gln Met Gln Ser Gln Ala Gly Gly Asn 450 455 460 Asn Thr Gly Ser Thr Pro Leu Arg Lys Ala Gln Ser Ser Ala Pro Lys 465 470 475 480 Val Arg Lys Ser Val Ser Ser Arg Ile His Glu Ala Val Lys Ala Ile 485 490 495 Val Leu Cys His Asn Val Thr Pro Val Tyr Glu Ser Arg Ala Gly Val 500 505 510 Thr Glu Glu Thr Glu Phe Ala Glu Ala Asp Gln Asp Phe Ser Asp Glu 515 520 525 Asn Arg Thr Tyr Gln Ala Ser Ser Pro Asp Glu Val Ala Leu Val Gln 530 535 540 Trp Thr Glu Ser Val Gly Leu Thr Leu Val Ser Arg Asp Leu Thr Ser 545 550 555 560 Met Gln Leu Lys Thr Pro Ser Gly Gln Val Leu Ser Phe Cys Ile Leu 565 570 575 Gln Leu Phe Pro Phe Thr Ser Glu Ser Lys Arg Met Gly Val Ile Val 580 585 590 Arg Asp Glu Ser Thr Ala Glu Ile Thr Phe Tyr Met Lys Gly Ala Asp 595 600 605 Val Ala Met Ser Pro Ile Val Gln Tyr Asn Asp Trp Leu Glu Glu Glu 610 615 620 Cys Gly Asn Met Ala Arg Glu Gly Leu Arg Thr Leu Val Val Ala Lys 625 630 635 640 Lys Ala Leu Thr Glu Glu Gln Tyr Gln Asp Phe Glu Ser Arg Tyr Thr 645 650 655 Gln Ala Lys Leu Ser Met His Asp Arg Ser Leu Lys Val Ala Ala Val 660 665 670 Val Glu Ser Leu Glu Arg Glu Met Glu Leu Leu Cys Leu Thr Gly Val 675 680 685 Glu Asp Gln Leu Gln Ala Asp Val Arg Pro Thr Leu Glu Met Leu Arg 690 695 700 Asn Ala Gly Ile Lys Ile Trp Met Leu Thr Gly Asp Lys Leu Glu Thr 705 710 715 720 Ala Thr Cys Ile Ala Lys Ser Ser His Leu Val Ser Arg Thr Gln Asp 725 730 735 Ile His Ile Phe Arg Gln Val Thr Ser Arg Gly Glu Ala His Leu Glu 740 745 750 Leu Asn Ala Phe Arg Arg Lys His Asp Cys Ala Leu Val Ile Ser Gly 755 760 765 Asp Ser Leu Glu Val Cys Leu Lys Tyr Tyr Glu His Glu Phe Val Glu 770 775 780 Leu Ala Cys Gln Cys Pro Ala Val Val Cys Cys Arg Cys Ser Pro Thr 785 790 795 800 Gln Lys Ala Arg Ile Val Thr Leu Leu Gln Gln His Thr Gly Arg Arg 805 810 815 Thr Cys Ala Ile Gly Asp Gly Gly Asn Asp Val Ser Met Ile Gln Ala 820 825 830 Ala Asp Cys Gly Ile Gly Ile Glu Gly Lys Glu Gly Lys Gln Ala Ser 835 840 845 Leu Ala Ala Asp Phe Ser Ile Thr Gln Phe Arg His Ile Gly Arg Leu 850 855 860 Leu Met Val His Gly Arg Asn Ser Tyr Lys Arg Ser Ala Ala Leu Gly 865 870 875 880 Gln Phe Val Met His Arg Gly Leu Ile Ile Ser Thr Met Gln Ala Val 885 890 895 Phe Ser Ser Val Phe Tyr Phe Ala Ser Val Pro Leu Tyr Gln Gly Phe 900 905 910 Leu Met Val Gly Tyr Ala Thr Ile Tyr Thr Met Phe Pro Val Phe Ser 915 920 925 Leu Val Leu Asp Gln Asp Val Lys Pro Glu Met Ala Met Leu Tyr Pro 930 935 940 Glu Leu Tyr Lys Asp Leu Thr Lys Gly Arg Ser Leu Ser Phe Lys Thr 945 950 955 960 Phe Leu Ile Trp Val Leu Ile Ser Ile Tyr Gln Gly Gly Ile Leu Met 965 970 975 Tyr Gly Ala Leu Val Leu Phe Glu Ser Glu Phe Val His Val Val Ala 980 985 990 Ile Ser Phe Thr Ala Leu Ile Leu Thr Glu Leu Leu Met Val Ala Leu 995 1000 1005 Thr Val Arg Thr Trp His Trp Leu Met Val Val Ala Glu Phe Leu Ser 1010 1015 1020 Leu Gly Cys Tyr Val Ser Ser Leu Ala Phe Leu Asn Glu Tyr Phe Asp 1025 1030 1035 1040 Val Ala Phe Ile Thr Thr Val Thr Phe Leu Trp Lys Val Ser Ala Ile 1045 1050 1055 Thr Val Val Ser Cys Leu Pro Leu Tyr Val Leu Lys Tyr Leu Arg Arg 1060 1065 1070 Lys Ser Ser Pro Pro Ser Tyr Cys Lys Leu Ala Ser 1075 1080 <210> SEQ ID NO 24 <211> LENGTH: 3255 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(3255) <400> SEQUENCE: 24 atg cca cta atg atg tct gaa gaa ggc ttt gag aat gag gaa agt gat 48 Met Pro Leu Met Met Ser Glu Glu Gly Phe Glu Asn Glu Glu Ser Asp 1 5 10 15 tac cac acc tta cca cga gcc agg ata atg caa agg aaa aga gga ctg 96 Tyr His Thr Leu Pro Arg Ala Arg Ile Met Gln Arg Lys Arg Gly Leu 20 25 30 gag tgg ttt gtc tgt gat ggc tgg aag ttc ctc tgt acc agt tgc tgt 144 Glu Trp Phe Val Cys Asp Gly Trp Lys Phe Leu Cys Thr Ser Cys Cys 35 40 45 ggt tgg ctg ata aat att tgt cga aga aag aaa gag ctg aaa gct cgc 192 Gly Trp Leu Ile Asn Ile Cys Arg Arg Lys Lys Glu Leu Lys Ala Arg 50 55 60 aca gta tgg ctt gga tgt cct gaa aag tgt gaa gaa aaa cat ccc agg 240 Thr Val Trp Leu Gly Cys Pro Glu Lys Cys Glu Glu Lys His Pro Arg 65 70 75 80 aat tct ata aaa aat caa aaa tac aat gtg ttt acc ttt ata cct ggg 288 Asn Ser Ile Lys Asn Gln Lys Tyr Asn Val Phe Thr Phe Ile Pro Gly 85 90 95 gtt ttg tat gaa caa ttc aag ttt ttc ttg aat ctc tat ttt cta gtg 336 Val Leu Tyr Glu Gln Phe Lys Phe Phe Leu Asn Leu Tyr Phe Leu Val 100 105 110 ata tcc tgc tca cag ttt gta cca gca ttg aaa ata ggc tat ctc tac 384 Ile Ser Cys Ser Gln Phe Val Pro Ala Leu Lys Ile Gly Tyr Leu Tyr 115 120 125 acc tac tgg gct cct ctg gga ttt gtc ttg gct gtt act atg aca cgg 432 Thr Tyr Trp Ala Pro Leu Gly Phe Val Leu Ala Val Thr Met Thr Arg 130 135 140 gaa gca att gat gaa ttt cgg cgt ttt cag cgt gac aag gaa gtg aat 480 Glu Ala Ile Asp Glu Phe Arg Arg Phe Gln Arg Asp Lys Glu Val Asn 145 150 155 160 tca caa cta tat agc aag ctt aca gta aga ggt aaa gtg caa gtt aag 528 Ser Gln Leu Tyr Ser Lys Leu Thr Val Arg Gly Lys Val Gln Val Lys 165 170 175 agt tca gac ata caa gtt gga gac ctc atc ata gtg gaa aag aat caa 576 Ser Ser Asp Ile Gln Val Gly Asp Leu Ile Ile Val Glu Lys Asn Gln 180 185 190 aga att cca tcg gac atg gtg ttt ctt agg act tca gaa aaa gca ggt 624 Arg Ile Pro Ser Asp Met Val Phe Leu Arg Thr Ser Glu Lys Ala Gly 195 200 205 tcg tgt ttt att cga act gat caa cta gat ggt gaa act gac tgg aag 672 Ser Cys Phe Ile Arg Thr Asp Gln Leu Asp Gly Glu Thr Asp Trp Lys 210 215 220 ctg aag gtg gca gtg agc tgc acg caa cag ctg ccg gct ctg ggg gac 720 Leu Lys Val Ala Val Ser Cys Thr Gln Gln Leu Pro Ala Leu Gly Asp 225 230 235 240 ctt ttt tct atc agt gct tat gtt tat gct cag aaa cca caa atg gac 768 Leu Phe Ser Ile Ser Ala Tyr Val Tyr Ala Gln Lys Pro Gln Met Asp 245 250 255 att cac agt ttc gaa ggc aca ttt acc agg gaa gac agt gac ccg ccc 816 Ile His Ser Phe Glu Gly Thr Phe Thr Arg Glu Asp Ser Asp Pro Pro 260 265 270 att cat gaa agt ctc agc ata gaa aat aca ttg tgg gca agc acc att 864 Ile His Glu Ser Leu Ser Ile Glu Asn Thr Leu Trp Ala Ser Thr Ile 275 280 285 gtt gca tca ggt act gta ata ggt gtt gtc att tat acc gga aaa gag 912 Val Ala Ser Gly Thr Val Ile Gly Val Val Ile Tyr Thr Gly Lys Glu 290 295 300 act cga agt gta atg aac aca tcc aat cca aaa aat aag gtt ggt ttg 960 Thr Arg Ser Val Met Asn Thr Ser Asn Pro Lys Asn Lys Val Gly Leu 305 310 315 320 ttg gac ctt gaa ctc aat cgg ctg acg aaa gcg cta ttt ttg gct tta 1008 Leu Asp Leu Glu Leu Asn Arg Leu Thr Lys Ala Leu Phe Leu Ala Leu 325 330 335 gtt gct ctt tcc att gtt atg gta acc tta caa gga ttt gtg ggt cca 1056 Val Ala Leu Ser Ile Val Met Val Thr Leu Gln Gly Phe Val Gly Pro 340 345 350 tgg tac cgc aat ctt ttt cgg ttc ctt ctc ctc ttt tct tac atc att 1104 Trp Tyr Arg Asn Leu Phe Arg Phe Leu Leu Leu Phe Ser Tyr Ile Ile 355 360 365 ccc ata agt ttg cgt gtg aac ttg gac atg ggc aaa gcg gtg tat gga 1152 Pro Ile Ser Leu Arg Val Asn Leu Asp Met Gly Lys Ala Val Tyr Gly 370 375 380 tgg atg atg atg aaa gat gag aac atc cct ggc acg gtc gtt cgg acc 1200 Trp Met Met Met Lys Asp Glu Asn Ile Pro Gly Thr Val Val Arg Thr 385 390 395 400 agc act atc cca gag gaa ctt ggg cgc ctg gtg tat tta ttg aca gac 1248 Ser Thr Ile Pro Glu Glu Leu Gly Arg Leu Val Tyr Leu Leu Thr Asp 405 410 415 aaa aca gga acc ctc acc cag aat gaa atg ata ttt aag cgg ctg cac 1296 Lys Thr Gly Thr Leu Thr Gln Asn Glu Met Ile Phe Lys Arg Leu His 420 425 430 ctg ggc acc gtg tcc tat ggc gcc gac acg atg gat gag atc cag agc 1344 Leu Gly Thr Val Ser Tyr Gly Ala Asp Thr Met Asp Glu Ile Gln Ser 435 440 445 cat gtc agg gac tcc tac tca cag atg cag tct caa gct ggt gga aac 1392 His Val Arg Asp Ser Tyr Ser Gln Met Gln Ser Gln Ala Gly Gly Asn 450 455 460 aat act ggt tca act cca cta aga aaa gcc caa tct tca gct ccc aaa 1440 Asn Thr Gly Ser Thr Pro Leu Arg Lys Ala Gln Ser Ser Ala Pro Lys 465 470 475 480 gtt agg aaa agt gtc agt agt cga atc cat gaa gcc gtg aaa gcc atc 1488 Val Arg Lys Ser Val Ser Ser Arg Ile His Glu Ala Val Lys Ala Ile 485 490 495 gtg ctg tgt cac aac gtg acc ccc gtg tat gag tct cgg gcc ggc gtt 1536 Val Leu Cys His Asn Val Thr Pro Val Tyr Glu Ser Arg Ala Gly Val 500 505 510 act gag gag act gag ttc gca gag gct gac caa gac ttc agt gat gag 1584 Thr Glu Glu Thr Glu Phe Ala Glu Ala Asp Gln Asp Phe Ser Asp Glu 515 520 525 aat cgc acc tac cag gct tcc agc ccg gat gag gtc gct ctg gtg cag 1632 Asn Arg Thr Tyr Gln Ala Ser Ser Pro Asp Glu Val Ala Leu Val Gln 530 535 540 tgg aca gag agt gtg ggc ctc acg ctg gtc agc agg gac ctc acc tcc 1680 Trp Thr Glu Ser Val Gly Leu Thr Leu Val Ser Arg Asp Leu Thr Ser 545 550 555 560 atg cag ctg aag acc ccc agt ggc cag gtc ctc agc ttc tgc att ctg 1728 Met Gln Leu Lys Thr Pro Ser Gly Gln Val Leu Ser Phe Cys Ile Leu 565 570 575 cag ctg ttt ccc ttc acc tcc gag agc aag cgg atg ggc gtc atc gtc 1776 Gln Leu Phe Pro Phe Thr Ser Glu Ser Lys Arg Met Gly Val Ile Val 580 585 590 agg gat gaa tcc acg gca gaa atc aca ttc tac atg aag ggc gct gac 1824 Arg Asp Glu Ser Thr Ala Glu Ile Thr Phe Tyr Met Lys Gly Ala Asp 595 600 605 gtg gcc atg tct cct atc gtg cag tat aat gac tgg ctg gaa gag gag 1872 Val Ala Met Ser Pro Ile Val Gln Tyr Asn Asp Trp Leu Glu Glu Glu 610 615 620 tgc gga aac atg gct cgc gaa gga ctg cgg acc ctc gtg gtt gca aag 1920 Cys Gly Asn Met Ala Arg Glu Gly Leu Arg Thr Leu Val Val Ala Lys 625 630 635 640 aag gcg ttg aca gag gag cag tac cag gac ttt gag agc cga tac act 1968 Lys Ala Leu Thr Glu Glu Gln Tyr Gln Asp Phe Glu Ser Arg Tyr Thr 645 650 655 caa gcc aag ctg agc atg cac gac agg tcc ctc aag gtg gcc gcg gta 2016 Gln Ala Lys Leu Ser Met His Asp Arg Ser Leu Lys Val Ala Ala Val 660 665 670 gtc gag agc ctg gag agg gag atg gaa ctg ctg tgc ctc acc ggc gtg 2064 Val Glu Ser Leu Glu Arg Glu Met Glu Leu Leu Cys Leu Thr Gly Val 675 680 685 gag gac cag ctg cag gca gac gtg cgg ccc acg ctg gag atg ctg cgc 2112 Glu Asp Gln Leu Gln Ala Asp Val Arg Pro Thr Leu Glu Met Leu Arg 690 695 700 aac gcc ggg atc aag ata tgg atg cta aca ggc gat aaa ctc gag aca 2160 Asn Ala Gly Ile Lys Ile Trp Met Leu Thr Gly Asp Lys Leu Glu Thr 705 710 715 720 gct acc tgc att gcc aaa agt tca cat ctc gtg tct aga aca caa gat 2208 Ala Thr Cys Ile Ala Lys Ser Ser His Leu Val Ser Arg Thr Gln Asp 725 730 735 att cat att ttc aga cag gta acc agt cgg gga gag gca cat ttg gag 2256 Ile His Ile Phe Arg Gln Val Thr Ser Arg Gly Glu Ala His Leu Glu 740 745 750 ctg aat gca ttt cga agg aag cat gat tgt gca cta gtc ata tct ggg 2304 Leu Asn Ala Phe Arg Arg Lys His Asp Cys Ala Leu Val Ile Ser Gly 755 760 765 gac tct ctg gag gtt tgt cta aag tac tac gag cat gaa ttt gtg gag 2352 Asp Ser Leu Glu Val Cys Leu Lys Tyr Tyr Glu His Glu Phe Val Glu 770 775 780 ctg gcc tgc cag tgc cct gcc gtg gtt tgc tgc cgc tgc tca ccc acc 2400 Leu Ala Cys Gln Cys Pro Ala Val Val Cys Cys Arg Cys Ser Pro Thr 785 790 795 800 cag aag gcc cgc att gtg aca ctg ctg cag cag cac aca ggg aga cgc 2448 Gln Lys Ala Arg Ile Val Thr Leu Leu Gln Gln His Thr Gly Arg Arg 805 810 815 acc tgc gcc atc ggt gat gga gga aat gat gtc agc atg att cag gca 2496 Thr Cys Ala Ile Gly Asp Gly Gly Asn Asp Val Ser Met Ile Gln Ala 820 825 830 gca gac tgt ggg att ggg att gag gga aag gag ggt aaa cag gcc tcg 2544 Ala Asp Cys Gly Ile Gly Ile Glu Gly Lys Glu Gly Lys Gln Ala Ser 835 840 845 ctg gcg gcc gac ttc tcc atc acg cag ttc cgg cac ata ggc agg ctg 2592 Leu Ala Ala Asp Phe Ser Ile Thr Gln Phe Arg His Ile Gly Arg Leu 850 855 860 ctc atg gtg cac ggg cgg aac agc tac aag agg tcg gcg gca ctc ggc 2640 Leu Met Val His Gly Arg Asn Ser Tyr Lys Arg Ser Ala Ala Leu Gly 865 870 875 880 cag ttc gtc atg cac agg ggc ctt atc atc tcc acc atg cag gct gtg 2688 Gln Phe Val Met His Arg Gly Leu Ile Ile Ser Thr Met Gln Ala Val 885 890 895 ttt tcc tca gtc ttc tac ttc gca tcc gtc cct ttg tat cag ggc ttc 2736 Phe Ser Ser Val Phe Tyr Phe Ala Ser Val Pro Leu Tyr Gln Gly Phe 900 905 910 ctc atg gtg ggg tat gcc acc ata tac acc atg ttc cca gtg ttc tcc 2784 Leu Met Val Gly Tyr Ala Thr Ile Tyr Thr Met Phe Pro Val Phe Ser 915 920 925 tta gtg ctg gac cag gac gtg aag cca gag atg gcg atg ctc tac ccg 2832 Leu Val Leu Asp Gln Asp Val Lys Pro Glu Met Ala Met Leu Tyr Pro 930 935 940 gag ctg tac aag gac ctc acc aag gga aga tcc ttg tcc ttc aaa acc 2880 Glu Leu Tyr Lys Asp Leu Thr Lys Gly Arg Ser Leu Ser Phe Lys Thr 945 950 955 960 ttc ctc atc tgg gtt tta ata agt att tac caa ggc ggc atc ctc atg 2928 Phe Leu Ile Trp Val Leu Ile Ser Ile Tyr Gln Gly Gly Ile Leu Met 965 970 975 tat ggg gcc ctg gtg ctc ttc gag tct gag ttc gtc cac gtg gtg gcc 2976 Tyr Gly Ala Leu Val Leu Phe Glu Ser Glu Phe Val His Val Val Ala 980 985 990 atc tcc ttc acc gca ctg atc ctg acc gag ctg ctg atg gtg gcg ctg 3024 Ile Ser Phe Thr Ala Leu Ile Leu Thr Glu Leu Leu Met Val Ala Leu 995 1000 1005 acc gtc cgc acg tgg cac tgg ctg atg gtg gtg gcc gag ttc ctc agc 3072 Thr Val Arg Thr Trp His Trp Leu Met Val Val Ala Glu Phe Leu Ser 1010 1015 1020 tta ggc tgc tac gtg tcc tca ctc gct ttt ctc aat gaa tat ttt gat 3120 Leu Gly Cys Tyr Val Ser Ser Leu Ala Phe Leu Asn Glu Tyr Phe Asp 1025 1030 1035 1040 gtt gcc ttt atc acc acc gtg acc ttc ctg tgg aaa gtg tcg gcg atc 3168 Val Ala Phe Ile Thr Thr Val Thr Phe Leu Trp Lys Val Ser Ala Ile 1045 1050 1055 acc gtg gtc agc tgc ctc ccg ctg tat gtc ctc aag tac ctg agg cgc 3216 Thr Val Val Ser Cys Leu Pro Leu Tyr Val Leu Lys Tyr Leu Arg Arg 1060 1065 1070 aag tct tct cct ccc agc tac tgc aag ctg gcc tcc taa 3255 Lys Ser Ser Pro Pro Ser Tyr Cys Lys Leu Ala Ser * 1075 1080 <210> SEQ ID NO 25 <211> LENGTH: 4231 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (156)...(3443) <400> SEQUENCE: 25 ggagtcgacc cacgcgtccg cattgagaca atgcctccac aaatacttga tgcaaaattc 60 agtaagacag cacttgttga atcaccatta tagtttctga caaattgttc tcaaaaaggt 120 accagctgga ggatgagtct gcgcatttgg atgaa atg cca cta atg atg tct 173 Met Pro Leu Met Met Ser 1 5 gaa gaa ggc ttt gag aat gag gaa agt gat tac cac acc tta cca cga 221 Glu Glu Gly Phe Glu Asn Glu Glu Ser Asp Tyr His Thr Leu Pro Arg 10 15 20 gcc agg ata atg caa agg aaa aga gga ctg gag tgg ttt gtc tgt gat 269 Ala Arg Ile Met Gln Arg Lys Arg Gly Leu Glu Trp Phe Val Cys Asp 25 30 35 ggc tgg aag ttc ctc tgt acc agt tgc tgt ggt tgg ctg ata aat att 317 Gly Trp Lys Phe Leu Cys Thr Ser Cys Cys Gly Trp Leu Ile Asn Ile 40 45 50 tgt cga aga aag aaa gag ctg aaa gct cgc aca gta tgg ctt gga tgt 365 Cys Arg Arg Lys Lys Glu Leu Lys Ala Arg Thr Val Trp Leu Gly Cys 55 60 65 70 cct gaa aag tgt gaa gaa aaa cat ccc agg aat tct ata aaa aat caa 413 Pro Glu Lys Cys Glu Glu Lys His Pro Arg Asn Ser Ile Lys Asn Gln 75 80 85 aaa tac aat gtg ttt acc ttt ata cct ggg gtt ttg tat gaa caa ttc 461 Lys Tyr Asn Val Phe Thr Phe Ile Pro Gly Val Leu Tyr Glu Gln Phe 90 95 100 aag ttt ttc ttg aat ctc tat ttt cta gtg ata tcc tgc tca cag ttt 509 Lys Phe Phe Leu Asn Leu Tyr Phe Leu Val Ile Ser Cys Ser Gln Phe 105 110 115 gta cca gca ttg aaa ata ggc tat ctc tac acc tac tgg gct cct ctg 557 Val Pro Ala Leu Lys Ile Gly Tyr Leu Tyr Thr Tyr Trp Ala Pro Leu 120 125 130 gga ttt gtc ttg gct gtt act atg aca cgg gaa gca att gat gaa ttt 605 Gly Phe Val Leu Ala Val Thr Met Thr Arg Glu Ala Ile Asp Glu Phe 135 140 145 150 cgg cgt ttt cag cgt gac aag gaa gtg aat tca caa cta tat agc aag 653 Arg Arg Phe Gln Arg Asp Lys Glu Val Asn Ser Gln Leu Tyr Ser Lys 155 160 165 ctt aca gta aga ggt aaa gtg caa gtt aag agt tca gac ata caa gtt 701 Leu Thr Val Arg Gly Lys Val Gln Val Lys Ser Ser Asp Ile Gln Val 170 175 180 gga gac ctc atc ata gtg gaa aag aat caa aga att cca tcg gac atg 749 Gly Asp Leu Ile Ile Val Glu Lys Asn Gln Arg Ile Pro Ser Asp Met 185 190 195 gtg ttt ctt agg act tca gaa aaa gca ggt tcg tgt ttt att cga act 797 Val Phe Leu Arg Thr Ser Glu Lys Ala Gly Ser Cys Phe Ile Arg Thr 200 205 210 gat caa cta gat ggt gaa act gac tgg aag ctg aag gtg gca gtg agc 845 Asp Gln Leu Asp Gly Glu Thr Asp Trp Lys Leu Lys Val Ala Val Ser 215 220 225 230 tgc acg caa cag ctg ccg gct ctg ggg gac ctt ttt tct atc agt gct 893 Cys Thr Gln Gln Leu Pro Ala Leu Gly Asp Leu Phe Ser Ile Ser Ala 235 240 245 tat gtt tat gct cag aaa cca caa atg gac att cac agt ttc gaa ggc 941 Tyr Val Tyr Ala Gln Lys Pro Gln Met Asp Ile His Ser Phe Glu Gly 250 255 260 aca ttt acc agg gaa gac agt gac ccg ccc att cat gaa agt ctc agc 989 Thr Phe Thr Arg Glu Asp Ser Asp Pro Pro Ile His Glu Ser Leu Ser 265 270 275 ata gaa aat aca ttg tgg gca agc acc att gtt gca tca ggt act gta 1037 Ile Glu Asn Thr Leu Trp Ala Ser Thr Ile Val Ala Ser Gly Thr Val 280 285 290 ata ggt gtt gtc att tat acc gga aaa gag act cga agt gta atg aac 1085 Ile Gly Val Val Ile Tyr Thr Gly Lys Glu Thr Arg Ser Val Met Asn 295 300 305 310 aca tcc aat cca aaa aat aag gtt ggt ttg ttg gac ctt gaa ctc aat 1133 Thr Ser Asn Pro Lys Asn Lys Val Gly Leu Leu Asp Leu Glu Leu Asn 315 320 325 cgg ctg acg aaa gcg cta ttt ttg gct tta gtt gct ctt tcc att gtt 1181 Arg Leu Thr Lys Ala Leu Phe Leu Ala Leu Val Ala Leu Ser Ile Val 330 335 340 atg gta acc tta caa gga ttt gtg ggt cca tgg tac cgc aat ctt ttt 1229 Met Val Thr Leu Gln Gly Phe Val Gly Pro Trp Tyr Arg Asn Leu Phe 345 350 355 cgg ttc ctt ctc ctc ttt tct tac atc att ccc ata agt ttg cgt gtg 1277 Arg Phe Leu Leu Leu Phe Ser Tyr Ile Ile Pro Ile Ser Leu Arg Val 360 365 370 aac ttg gac atg ggc aaa gcg gtg tat gga tgg atg atg atg aaa gat 1325 Asn Leu Asp Met Gly Lys Ala Val Tyr Gly Trp Met Met Met Lys Asp 375 380 385 390 gag aac atc cct ggc acg gtc gtt cgg acc agc act atc cca gag gaa 1373 Glu Asn Ile Pro Gly Thr Val Val Arg Thr Ser Thr Ile Pro Glu Glu 395 400 405 ctt ggg cgc ctg gtg tat tta ttg aca gac aaa aca gga acc ctc acc 1421 Leu Gly Arg Leu Val Tyr Leu Leu Thr Asp Lys Thr Gly Thr Leu Thr 410 415 420 cag aat gaa atg ata ttt aag cgg ctg cac ctg ggc acc gtg tcc tat 1469 Gln Asn Glu Met Ile Phe Lys Arg Leu His Leu Gly Thr Val Ser Tyr 425 430 435 ggc gcc gac acg atg gat gag atc cag agc cat gtc agg gac tcc tac 1517 Gly Ala Asp Thr Met Asp Glu Ile Gln Ser His Val Arg Asp Ser Tyr 440 445 450 tca cag atg cag tct caa gct ggt gga aac aat act ggt tca act cca 1565 Ser Gln Met Gln Ser Gln Ala Gly Gly Asn Asn Thr Gly Ser Thr Pro 455 460 465 470 cta aga aaa gcc caa tct tca gct ccc aaa gtt agg aaa agt gtc agt 1613 Leu Arg Lys Ala Gln Ser Ser Ala Pro Lys Val Arg Lys Ser Val Ser 475 480 485 agt cga atc cat gaa gcc gtg aaa gcc atc gtg ctg tgt cac aac gtg 1661 Ser Arg Ile His Glu Ala Val Lys Ala Ile Val Leu Cys His Asn Val 490 495 500 acc ccc gtg tat gag tct cgg gcc ggc gtt act gag gag act gag ttc 1709 Thr Pro Val Tyr Glu Ser Arg Ala Gly Val Thr Glu Glu Thr Glu Phe 505 510 515 gca gag gct gac caa gac ttc agt gat gag aat cgc acc tac cag gct 1757 Ala Glu Ala Asp Gln Asp Phe Ser Asp Glu Asn Arg Thr Tyr Gln Ala 520 525 530 tcc agc ccg gat gag gtc gct ctg gtg cag tgg aca gag agt gtg ggc 1805 Ser Ser Pro Asp Glu Val Ala Leu Val Gln Trp Thr Glu Ser Val Gly 535 540 545 550 ctc acg ctg gtc agc agg gac ctc acc tcc atg cag ctg aag acc ccc 1853 Leu Thr Leu Val Ser Arg Asp Leu Thr Ser Met Gln Leu Lys Thr Pro 555 560 565 agt ggc cag gtc ctc agc ttc tgc att ctg cag ctg ttt ccc ttc acc 1901 Ser Gly Gln Val Leu Ser Phe Cys Ile Leu Gln Leu Phe Pro Phe Thr 570 575 580 tcc gag agc aag cgg atg ggc gtc atc gtc agg gat gaa tcc acg gca 1949 Ser Glu Ser Lys Arg Met Gly Val Ile Val Arg Asp Glu Ser Thr Ala 585 590 595 gaa atc aca ttc tac atg aag ggc gct gac gtg gcc atg tct cct atc 1997 Glu Ile Thr Phe Tyr Met Lys Gly Ala Asp Val Ala Met Ser Pro Ile 600 605 610 gtg cag tat aat gac tgg ctg gaa gag gag tgc gga aac atg gct cgc 2045 Val Gln Tyr Asn Asp Trp Leu Glu Glu Glu Cys Gly Asn Met Ala Arg 615 620 625 630 gaa gga ctg cgg acc ctc gtg gtt gca aag aag gcg ttg aca gag gag 2093 Glu Gly Leu Arg Thr Leu Val Val Ala Lys Lys Ala Leu Thr Glu Glu 635 640 645 cag tac cag gac ttt gag agc cga tac act caa gcc aag ctg agc atg 2141 Gln Tyr Gln Asp Phe Glu Ser Arg Tyr Thr Gln Ala Lys Leu Ser Met 650 655 660 cac gac agg tcc ctc aag gtg gcc gcg gta gtc gag agc ctg gag agg 2189 His Asp Arg Ser Leu Lys Val Ala Ala Val Val Glu Ser Leu Glu Arg 665 670 675 gag atg gaa ctg ctg tgc ctc acc ggc gtg gag gac cag ctg cag gca 2237 Glu Met Glu Leu Leu Cys Leu Thr Gly Val Glu Asp Gln Leu Gln Ala 680 685 690 gac gtg cgg ccc acg ctg gag atg ctg cgc aac gcc ggg atc aag ata 2285 Asp Val Arg Pro Thr Leu Glu Met Leu Arg Asn Ala Gly Ile Lys Ile 695 700 705 710 tgg atg cta aca ggc gat aaa ctc gag aca gct acc tgc att gcc aaa 2333 Trp Met Leu Thr Gly Asp Lys Leu Glu Thr Ala Thr Cys Ile Ala Lys 715 720 725 agt tca cat ctc gtg tct aga aca caa gat att cat att ttc aga cag 2381 Ser Ser His Leu Val Ser Arg Thr Gln Asp Ile His Ile Phe Arg Gln 730 735 740 gta acc agt cgg gga gag gca cat ttg gag ctg aat gca ttt cga agg 2429 Val Thr Ser Arg Gly Glu Ala His Leu Glu Leu Asn Ala Phe Arg Arg 745 750 755 aag cat gat tgt gca cta gtc ata tct ggg gac tct ctg gag gtt tgt 2477 Lys His Asp Cys Ala Leu Val Ile Ser Gly Asp Ser Leu Glu Val Cys 760 765 770 cta aag tac tac gag cat gaa ttt gtg gag ctg gcc tgc cag tgc cct 2525 Leu Lys Tyr Tyr Glu His Glu Phe Val Glu Leu Ala Cys Gln Cys Pro 775 780 785 790 gcc gtg gtt tgc tgc cgc tgc tca ccc acc cag aag gcc cgc att gtg 2573 Ala Val Val Cys Cys Arg Cys Ser Pro Thr Gln Lys Ala Arg Ile Val 795 800 805 aca ctg ctg cag cag cac aca ggg aga cgc acc tgc gcc atc ggt gat 2621 Thr Leu Leu Gln Gln His Thr Gly Arg Arg Thr Cys Ala Ile Gly Asp 810 815 820 gga gga aat gat gtc agc atg att cag gca gca gac tgt ggg att ggg 2669 Gly Gly Asn Asp Val Ser Met Ile Gln Ala Ala Asp Cys Gly Ile Gly 825 830 835 att gag gga aag gag ggt aaa cag gcc tcg ctg gcg gcc gac ttc tcc 2717 Ile Glu Gly Lys Glu Gly Lys Gln Ala Ser Leu Ala Ala Asp Phe Ser 840 845 850 atc acg cag ttc cgg cac ata ggc agg ctg ctc atg gtg cac ggg cgg 2765 Ile Thr Gln Phe Arg His Ile Gly Arg Leu Leu Met Val His Gly Arg 855 860 865 870 aac agc tac aag agg tcg gcg gca ctc ggc cag ttc gtc atg cac agg 2813 Asn Ser Tyr Lys Arg Ser Ala Ala Leu Gly Gln Phe Val Met His Arg 875 880 885 ggc ctt atc atc tcc acc atg cag gct gtg ttt tcc tca gtc ttc tac 2861 Gly Leu Ile Ile Ser Thr Met Gln Ala Val Phe Ser Ser Val Phe Tyr 890 895 900 ttc gca tcc gtc cct ttg tat cag ggc ttc ctc atg gtg ggg tat gcc 2909 Phe Ala Ser Val Pro Leu Tyr Gln Gly Phe Leu Met Val Gly Tyr Ala 905 910 915 acc ata tac acc atg ttc cca gtg ttc tcc tta gtg ctg gac cag gac 2957 Thr Ile Tyr Thr Met Phe Pro Val Phe Ser Leu Val Leu Asp Gln Asp 920 925 930 gtg aag cca gag atg gcg atg ctc tac ccg gag ctg tac aag gac ctc 3005 Val Lys Pro Glu Met Ala Met Leu Tyr Pro Glu Leu Tyr Lys Asp Leu 935 940 945 950 acc aag gga aga tcc ttg tcc ttc aaa acc ttc ctc atc tgg gtt tta 3053 Thr Lys Gly Arg Ser Leu Ser Phe Lys Thr Phe Leu Ile Trp Val Leu 955 960 965 ata agt att tac caa ggc ggc atc ctc atg tat ggg gcc ctg gtg ctc 3101 Ile Ser Ile Tyr Gln Gly Gly Ile Leu Met Tyr Gly Ala Leu Val Leu 970 975 980 ttc gag tct gag ttc gtc cac gtg gtg gcc atc tcc ttc acc gca ctg 3149 Phe Glu Ser Glu Phe Val His Val Val Ala Ile Ser Phe Thr Ala Leu 985 990 995 atc ctg acc gag ctg ctg atg gtg gcg ctg acc gtc cgc acg tgg cac 3197 Ile Leu Thr Glu Leu Leu Met Val Ala Leu Thr Val Arg Thr Trp His 1000 1005 1010 tgg ctg atg gtg gtg gcc gag ttc ctc agc tta ggc tgc tac gtg tcc 3245 Trp Leu Met Val Val Ala Glu Phe Leu Ser Leu Gly Cys Tyr Val Ser 1015 1020 1025 1030 tca ctc gct ttt ctc aat gaa tat ttt ggt ata ggc aga gtg tct ttt 3293 Ser Leu Ala Phe Leu Asn Glu Tyr Phe Gly Ile Gly Arg Val Ser Phe 1035 1040 1045 gga gct ttc tta gat gtt gcc ttt atc acc acc gtg acc ttc ctg tgg 3341 Gly Ala Phe Leu Asp Val Ala Phe Ile Thr Thr Val Thr Phe Leu Trp 1050 1055 1060 aaa gtg tcg gcg atc acc gtg gtc agc tgc ctc ccg ctg tat gtc ctc 3389 Lys Val Ser Ala Ile Thr Val Val Ser Cys Leu Pro Leu Tyr Val Leu 1065 1070 1075 aag tac ctg agg cgc aag tct tct cct ccc agc tac tgc aag ctg gcc 3437 Lys Tyr Leu Arg Arg Lys Ser Ser Pro Pro Ser Tyr Cys Lys Leu Ala 1080 1085 1090 tcc taa ggggctgtgc acccccagcg ggctggcccc agcaccttct gcccttccca 3493 Ser * 1095 gcaccttgtg cccttgccag tgaacgcagg gtttgccatt gctaccaagc aagcaccaca 3553 agaaagggag ggtacgccag gcgagcccag ggcacagatg ctgagacagc ctctccttct 3613 cagtgcaggg acgtcacccc tgccaggcaa gcccagggca cagatgccag gatggcttct 3673 ccctctcagt gcgaggcttc acccctgcca ggcaagccca gggcatagat gctgagacag 3733 cctctccctc tcagtgcagg gacgtcaccc ctgccaggca agcccagggc acagaggccg 3793 ggacggcctc tccctctcag tgtgaggctt cacccatgct aggcaagccc agggcacaga 3853 tgccgggatg gcccctccct ctcagtgcgg gaacgtcacc cctgccaggc aagcccaggg 3913 cacagatgct gcgatggcct cttcctctta agtgtggggc ctcacccctg cttttctttc 3973 tttttttgta ttgtcaaaat tgtatttcca tattgaagca gcttgagttt ctactgaaaa 4033 tgagcccgaa ttatttcact attactgtaa agggttcatc ttactctggc attctgagaa 4093 ttagactgaa agtttaattt ctgcagttcc ctcatattca gattctttct ttgatgttat 4153 aacacaaagt cattcctact caaatgtaat aaaattgagg ctccacggag aaaaaaaaaa 4213 aaaaaaaaaa aaaaaaaa 4231 <210> SEQ ID NO 26 <211> LENGTH: 1095 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 26 Met Pro Leu Met Met Ser Glu Glu Gly Phe Glu Asn Glu Glu Ser Asp 1 5 10 15 Tyr His Thr Leu Pro Arg Ala Arg Ile Met Gln Arg Lys Arg Gly Leu 20 25 30 Glu Trp Phe Val Cys Asp Gly Trp Lys Phe Leu Cys Thr Ser Cys Cys 35 40 45 Gly Trp Leu Ile Asn Ile Cys Arg Arg Lys Lys Glu Leu Lys Ala Arg 50 55 60 Thr Val Trp Leu Gly Cys Pro Glu Lys Cys Glu Glu Lys His Pro Arg 65 70 75 80 Asn Ser Ile Lys Asn Gln Lys Tyr Asn Val Phe Thr Phe Ile Pro Gly 85 90 95 Val Leu Tyr Glu Gln Phe Lys Phe Phe Leu Asn Leu Tyr Phe Leu Val 100 105 110 Ile Ser Cys Ser Gln Phe Val Pro Ala Leu Lys Ile Gly Tyr Leu Tyr 115 120 125 Thr Tyr Trp Ala Pro Leu Gly Phe Val Leu Ala Val Thr Met Thr Arg 130 135 140 Glu Ala Ile Asp Glu Phe Arg Arg Phe Gln Arg Asp Lys Glu Val Asn 145 150 155 160 Ser Gln Leu Tyr Ser Lys Leu Thr Val Arg Gly Lys Val Gln Val Lys 165 170 175 Ser Ser Asp Ile Gln Val Gly Asp Leu Ile Ile Val Glu Lys Asn Gln 180 185 190 Arg Ile Pro Ser Asp Met Val Phe Leu Arg Thr Ser Glu Lys Ala Gly 195 200 205 Ser Cys Phe Ile Arg Thr Asp Gln Leu Asp Gly Glu Thr Asp Trp Lys 210 215 220 Leu Lys Val Ala Val Ser Cys Thr Gln Gln Leu Pro Ala Leu Gly Asp 225 230 235 240 Leu Phe Ser Ile Ser Ala Tyr Val Tyr Ala Gln Lys Pro Gln Met Asp 245 250 255 Ile His Ser Phe Glu Gly Thr Phe Thr Arg Glu Asp Ser Asp Pro Pro 260 265 270 Ile His Glu Ser Leu Ser Ile Glu Asn Thr Leu Trp Ala Ser Thr Ile 275 280 285 Val Ala Ser Gly Thr Val Ile Gly Val Val Ile Tyr Thr Gly Lys Glu 290 295 300 Thr Arg Ser Val Met Asn Thr Ser Asn Pro Lys Asn Lys Val Gly Leu 305 310 315 320 Leu Asp Leu Glu Leu Asn Arg Leu Thr Lys Ala Leu Phe Leu Ala Leu 325 330 335 Val Ala Leu Ser Ile Val Met Val Thr Leu Gln Gly Phe Val Gly Pro 340 345 350 Trp Tyr Arg Asn Leu Phe Arg Phe Leu Leu Leu Phe Ser Tyr Ile Ile 355 360 365 Pro Ile Ser Leu Arg Val Asn Leu Asp Met Gly Lys Ala Val Tyr Gly 370 375 380 Trp Met Met Met Lys Asp Glu Asn Ile Pro Gly Thr Val Val Arg Thr 385 390 395 400 Ser Thr Ile Pro Glu Glu Leu Gly Arg Leu Val Tyr Leu Leu Thr Asp 405 410 415 Lys Thr Gly Thr Leu Thr Gln Asn Glu Met Ile Phe Lys Arg Leu His 420 425 430 Leu Gly Thr Val Ser Tyr Gly Ala Asp Thr Met Asp Glu Ile Gln Ser 435 440 445 His Val Arg Asp Ser Tyr Ser Gln Met Gln Ser Gln Ala Gly Gly Asn 450 455 460 Asn Thr Gly Ser Thr Pro Leu Arg Lys Ala Gln Ser Ser Ala Pro Lys 465 470 475 480 Val Arg Lys Ser Val Ser Ser Arg Ile His Glu Ala Val Lys Ala Ile 485 490 495 Val Leu Cys His Asn Val Thr Pro Val Tyr Glu Ser Arg Ala Gly Val 500 505 510 Thr Glu Glu Thr Glu Phe Ala Glu Ala Asp Gln Asp Phe Ser Asp Glu 515 520 525 Asn Arg Thr Tyr Gln Ala Ser Ser Pro Asp Glu Val Ala Leu Val Gln 530 535 540 Trp Thr Glu Ser Val Gly Leu Thr Leu Val Ser Arg Asp Leu Thr Ser 545 550 555 560 Met Gln Leu Lys Thr Pro Ser Gly Gln Val Leu Ser Phe Cys Ile Leu 565 570 575 Gln Leu Phe Pro Phe Thr Ser Glu Ser Lys Arg Met Gly Val Ile Val 580 585 590 Arg Asp Glu Ser Thr Ala Glu Ile Thr Phe Tyr Met Lys Gly Ala Asp 595 600 605 Val Ala Met Ser Pro Ile Val Gln Tyr Asn Asp Trp Leu Glu Glu Glu 610 615 620 Cys Gly Asn Met Ala Arg Glu Gly Leu Arg Thr Leu Val Val Ala Lys 625 630 635 640 Lys Ala Leu Thr Glu Glu Gln Tyr Gln Asp Phe Glu Ser Arg Tyr Thr 645 650 655 Gln Ala Lys Leu Ser Met His Asp Arg Ser Leu Lys Val Ala Ala Val 660 665 670 Val Glu Ser Leu Glu Arg Glu Met Glu Leu Leu Cys Leu Thr Gly Val 675 680 685 Glu Asp Gln Leu Gln Ala Asp Val Arg Pro Thr Leu Glu Met Leu Arg 690 695 700 Asn Ala Gly Ile Lys Ile Trp Met Leu Thr Gly Asp Lys Leu Glu Thr 705 710 715 720 Ala Thr Cys Ile Ala Lys Ser Ser His Leu Val Ser Arg Thr Gln Asp 725 730 735 Ile His Ile Phe Arg Gln Val Thr Ser Arg Gly Glu Ala His Leu Glu 740 745 750 Leu Asn Ala Phe Arg Arg Lys His Asp Cys Ala Leu Val Ile Ser Gly 755 760 765 Asp Ser Leu Glu Val Cys Leu Lys Tyr Tyr Glu His Glu Phe Val Glu 770 775 780 Leu Ala Cys Gln Cys Pro Ala Val Val Cys Cys Arg Cys Ser Pro Thr 785 790 795 800 Gln Lys Ala Arg Ile Val Thr Leu Leu Gln Gln His Thr Gly Arg Arg 805 810 815 Thr Cys Ala Ile Gly Asp Gly Gly Asn Asp Val Ser Met Ile Gln Ala 820 825 830 Ala Asp Cys Gly Ile Gly Ile Glu Gly Lys Glu Gly Lys Gln Ala Ser 835 840 845 Leu Ala Ala Asp Phe Ser Ile Thr Gln Phe Arg His Ile Gly Arg Leu 850 855 860 Leu Met Val His Gly Arg Asn Ser Tyr Lys Arg Ser Ala Ala Leu Gly 865 870 875 880 Gln Phe Val Met His Arg Gly Leu Ile Ile Ser Thr Met Gln Ala Val 885 890 895 Phe Ser Ser Val Phe Tyr Phe Ala Ser Val Pro Leu Tyr Gln Gly Phe 900 905 910 Leu Met Val Gly Tyr Ala Thr Ile Tyr Thr Met Phe Pro Val Phe Ser 915 920 925 Leu Val Leu Asp Gln Asp Val Lys Pro Glu Met Ala Met Leu Tyr Pro 930 935 940 Glu Leu Tyr Lys Asp Leu Thr Lys Gly Arg Ser Leu Ser Phe Lys Thr 945 950 955 960 Phe Leu Ile Trp Val Leu Ile Ser Ile Tyr Gln Gly Gly Ile Leu Met 965 970 975 Tyr Gly Ala Leu Val Leu Phe Glu Ser Glu Phe Val His Val Val Ala 980 985 990 Ile Ser Phe Thr Ala Leu Ile Leu Thr Glu Leu Leu Met Val Ala Leu 995 1000 1005 Thr Val Arg Thr Trp His Trp Leu Met Val Val Ala Glu Phe Leu Ser 1010 1015 1020 Leu Gly Cys Tyr Val Ser Ser Leu Ala Phe Leu Asn Glu Tyr Phe Gly 1025 1030 1035 1040 Ile Gly Arg Val Ser Phe Gly Ala Phe Leu Asp Val Ala Phe Ile Thr 1045 1050 1055 Thr Val Thr Phe Leu Trp Lys Val Ser Ala Ile Thr Val Val Ser Cys 1060 1065 1070 Leu Pro Leu Tyr Val Leu Lys Tyr Leu Arg Arg Lys Ser Ser Pro Pro 1075 1080 1085 Ser Tyr Cys Lys Leu Ala Ser 1090 1095 <210> SEQ ID NO 27 <211> LENGTH: 3255 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (1)...(3255) <400> SEQUENCE: 27 atg cca cta atg atg tct gaa gaa ggc ttt gag aat gag gaa agt gat 48 Met Pro Leu Met Met Ser Glu Glu Gly Phe Glu Asn Glu Glu Ser Asp 1 5 10 15 tac cac acc tta cca cga gcc agg ata atg caa agg aaa aga gga ctg 96 Tyr His Thr Leu Pro Arg Ala Arg Ile Met Gln Arg Lys Arg Gly Leu 20 25 30 gag tgg ttt gtc tgt gat ggc tgg aag ttc ctc tgt acc agt tgc tgt 144 Glu Trp Phe Val Cys Asp Gly Trp Lys Phe Leu Cys Thr Ser Cys Cys 35 40 45 ggt tgg ctg ata aat att tgt cga aga aag aaa gag ctg aaa gct cgc 192 Gly Trp Leu Ile Asn Ile Cys Arg Arg Lys Lys Glu Leu Lys Ala Arg 50 55 60 aca gta tgg ctt gga tgt cct gaa aag tgt gaa gaa aaa cat ccc agg 240 Thr Val Trp Leu Gly Cys Pro Glu Lys Cys Glu Glu Lys His Pro Arg 65 70 75 80 aat tct ata aaa aat caa aaa tac aat gtg ttt acc ttt ata cct ggg 288 Asn Ser Ile Lys Asn Gln Lys Tyr Asn Val Phe Thr Phe Ile Pro Gly 85 90 95 gtt ttg tat gaa caa ttc aag ttt ttc ttg aat ctc tat ttt cta gtg 336 Val Leu Tyr Glu Gln Phe Lys Phe Phe Leu Asn Leu Tyr Phe Leu Val 100 105 110 ata tcc tgc tca cag ttt gta cca gca ttg aaa ata ggc tat ctc tac 384 Ile Ser Cys Ser Gln Phe Val Pro Ala Leu Lys Ile Gly Tyr Leu Tyr 115 120 125 acc tac tgg gct cct ctg gga ttt gtc ttg gct gtt act atg aca cgg 432 Thr Tyr Trp Ala Pro Leu Gly Phe Val Leu Ala Val Thr Met Thr Arg 130 135 140 gaa gca att gat gaa ttt cgg cgt ttt cag cgt gac aag gaa gtg aat 480 Glu Ala Ile Asp Glu Phe Arg Arg Phe Gln Arg Asp Lys Glu Val Asn 145 150 155 160 tca caa cta tat agc aag ctt aca gta aga ggt aaa gtg caa gtt aag 528 Ser Gln Leu Tyr Ser Lys Leu Thr Val Arg Gly Lys Val Gln Val Lys 165 170 175 agt tca gac ata caa gtt gga gac ctc atc ata gtg gaa aag aat caa 576 Ser Ser Asp Ile Gln Val Gly Asp Leu Ile Ile Val Glu Lys Asn Gln 180 185 190 aga att cca tcg gac atg gtg ttt ctt agg act tca gaa aaa gca ggt 624 Arg Ile Pro Ser Asp Met Val Phe Leu Arg Thr Ser Glu Lys Ala Gly 195 200 205 tcg tgt ttt att cga act gat caa cta gat ggt gaa act gac tgg aag 672 Ser Cys Phe Ile Arg Thr Asp Gln Leu Asp Gly Glu Thr Asp Trp Lys 210 215 220 ctg aag gtg gca gtg agc tgc acg caa cag ctg ccg gct ctg ggg gac 720 Leu Lys Val Ala Val Ser Cys Thr Gln Gln Leu Pro Ala Leu Gly Asp 225 230 235 240 ctt ttt tct atc agt gct tat gtt tat gct cag aaa cca caa atg gac 768 Leu Phe Ser Ile Ser Ala Tyr Val Tyr Ala Gln Lys Pro Gln Met Asp 245 250 255 att cac agt ttc gaa ggc aca ttt acc agg gaa gac agt gac ccg ccc 816 Ile His Ser Phe Glu Gly Thr Phe Thr Arg Glu Asp Ser Asp Pro Pro 260 265 270 att cat gaa agt ctc agc ata gaa aat aca ttg tgg gca agc acc att 864 Ile His Glu Ser Leu Ser Ile Glu Asn Thr Leu Trp Ala Ser Thr Ile 275 280 285 gtt gca tca ggt act gta ata ggt gtt gtc att tat acc gga aaa gag 912 Val Ala Ser Gly Thr Val Ile Gly Val Val Ile Tyr Thr Gly Lys Glu 290 295 300 act cga agt gta atg aac aca tcc aat cca aaa aat aag gtt ggt ttg 960 Thr Arg Ser Val Met Asn Thr Ser Asn Pro Lys Asn Lys Val Gly Leu 305 310 315 320 ttg gac ctt gaa ctc aat cgg ctg acg aaa gcg cta ttt ttg gct tta 1008 Leu Asp Leu Glu Leu Asn Arg Leu Thr Lys Ala Leu Phe Leu Ala Leu 325 330 335 gtt gct ctt tcc att gtt atg gta acc tta caa gga ttt gtg ggt cca 1056 Val Ala Leu Ser Ile Val Met Val Thr Leu Gln Gly Phe Val Gly Pro 340 345 350 tgg tac cgc aat ctt ttt cgg ttc ctt ctc ctc ttt tct tac atc att 1104 Trp Tyr Arg Asn Leu Phe Arg Phe Leu Leu Leu Phe Ser Tyr Ile Ile 355 360 365 ccc ata agt ttg cgt gtg aac ttg gac atg ggc aaa gcg gtg tat gga 1152 Pro Ile Ser Leu Arg Val Asn Leu Asp Met Gly Lys Ala Val Tyr Gly 370 375 380 tgg atg atg atg aaa gat gag aac atc cct ggc acg gtc gtt cgg acc 1200 Trp Met Met Met Lys Asp Glu Asn Ile Pro Gly Thr Val Val Arg Thr 385 390 395 400 agc act atc cca gag gaa ctt ggg cgc ctg gtg tat tta ttg aca gac 1248 Ser Thr Ile Pro Glu Glu Leu Gly Arg Leu Val Tyr Leu Leu Thr Asp 405 410 415 aaa aca gga acc ctc acc cag aat gaa atg ata ttt aag cgg ctg cac 1296 Lys Thr Gly Thr Leu Thr Gln Asn Glu Met Ile Phe Lys Arg Leu His 420 425 430 ctg ggc acc gtg tcc tat ggc gcc gac acg atg gat gag atc cag agc 1344 Leu Gly Thr Val Ser Tyr Gly Ala Asp Thr Met Asp Glu Ile Gln Ser 435 440 445 cat gtc agg gac tcc tac tca cag atg cag tct caa gct ggt gga aac 1392 His Val Arg Asp Ser Tyr Ser Gln Met Gln Ser Gln Ala Gly Gly Asn 450 455 460 aat act ggt tca act cca cta aga aaa gcc caa tct tca gct ccc aaa 1440 Asn Thr Gly Ser Thr Pro Leu Arg Lys Ala Gln Ser Ser Ala Pro Lys 465 470 475 480 gtt agg aaa agt gtc agt agt cga atc cat gaa gcc gtg aaa gcc atc 1488 Val Arg Lys Ser Val Ser Ser Arg Ile His Glu Ala Val Lys Ala Ile 485 490 495 gtg ctg tgt cac aac gtg acc ccc gtg tat gag tct cgg gcc ggc gtt 1536 Val Leu Cys His Asn Val Thr Pro Val Tyr Glu Ser Arg Ala Gly Val 500 505 510 act gag gag act gag ttc gca gag gct gac caa gac ttc agt gat gag 1584 Thr Glu Glu Thr Glu Phe Ala Glu Ala Asp Gln Asp Phe Ser Asp Glu 515 520 525 aat cgc acc tac cag gct tcc agc ccg gat gag gtc gct ctg gtg cag 1632 Asn Arg Thr Tyr Gln Ala Ser Ser Pro Asp Glu Val Ala Leu Val Gln 530 535 540 tgg aca gag agt gtg ggc ctc acg ctg gtc agc agg gac ctc acc tcc 1680 Trp Thr Glu Ser Val Gly Leu Thr Leu Val Ser Arg Asp Leu Thr Ser 545 550 555 560 atg cag ctg aag acc ccc agt ggc cag gtc ctc agc ttc tgc att ctg 1728 Met Gln Leu Lys Thr Pro Ser Gly Gln Val Leu Ser Phe Cys Ile Leu 565 570 575 cag ctg ttt ccc ttc acc tcc gag agc aag cgg atg ggc gtc atc gtc 1776 Gln Leu Phe Pro Phe Thr Ser Glu Ser Lys Arg Met Gly Val Ile Val 580 585 590 agg gat gaa tcc acg gca gaa atc aca ttc tac atg aag ggc gct gac 1824 Arg Asp Glu Ser Thr Ala Glu Ile Thr Phe Tyr Met Lys Gly Ala Asp 595 600 605 gtg gcc atg tct cct atc gtg cag tat aat gac tgg ctg gaa gag gag 1872 Val Ala Met Ser Pro Ile Val Gln Tyr Asn Asp Trp Leu Glu Glu Glu 610 615 620 tgc gga aac atg gct cgc gaa gga ctg cgg acc ctc gtg gtt gca aag 1920 Cys Gly Asn Met Ala Arg Glu Gly Leu Arg Thr Leu Val Val Ala Lys 625 630 635 640 aag gcg ttg aca gag gag cag tac cag gac ttt gag agc cga tac act 1968 Lys Ala Leu Thr Glu Glu Gln Tyr Gln Asp Phe Glu Ser Arg Tyr Thr 645 650 655 caa gcc aag ctg agc atg cac gac agg tcc ctc aag gtg gcc gcg gta 2016 Gln Ala Lys Leu Ser Met His Asp Arg Ser Leu Lys Val Ala Ala Val 660 665 670 gtc gag agc ctg gag agg gag atg gaa ctg ctg tgc ctc acc ggc gtg 2064 Val Glu Ser Leu Glu Arg Glu Met Glu Leu Leu Cys Leu Thr Gly Val 675 680 685 gag gac cag ctg cag gca gac gtg cgg ccc acg ctg gag atg ctg cgc 2112 Glu Asp Gln Leu Gln Ala Asp Val Arg Pro Thr Leu Glu Met Leu Arg 690 695 700 aac gcc ggg atc aag ata tgg atg cta aca ggc gat aaa ctc gag aca 2160 Asn Ala Gly Ile Lys Ile Trp Met Leu Thr Gly Asp Lys Leu Glu Thr 705 710 715 720 gct acc tgc att gcc aaa agt tca cat ctc gtg tct aga aca caa gat 2208 Ala Thr Cys Ile Ala Lys Ser Ser His Leu Val Ser Arg Thr Gln Asp 725 730 735 att cat att ttc aga cag gta acc agt cgg gga gag gca cat ttg gag 2256 Ile His Ile Phe Arg Gln Val Thr Ser Arg Gly Glu Ala His Leu Glu 740 745 750 ctg aat gca ttt cga agg aag cat gat tgt gca cta gtc ata tct ggg 2304 Leu Asn Ala Phe Arg Arg Lys His Asp Cys Ala Leu Val Ile Ser Gly 755 760 765 gac tct ctg gag gtt tgt cta aag tac tac gag cat gaa ttt gtg gag 2352 Asp Ser Leu Glu Val Cys Leu Lys Tyr Tyr Glu His Glu Phe Val Glu 770 775 780 ctg gcc tgc cag tgc cct gcc gtg gtt tgc tgc cgc tgc tca ccc acc 2400 Leu Ala Cys Gln Cys Pro Ala Val Val Cys Cys Arg Cys Ser Pro Thr 785 790 795 800 cag aag gcc cgc att gtg aca ctg ctg cag cag cac aca ggg aga cgc 2448 Gln Lys Ala Arg Ile Val Thr Leu Leu Gln Gln His Thr Gly Arg Arg 805 810 815 acc tgc gcc atc ggt gat gga gga aat gat gtc agc atg att cag gca 2496 Thr Cys Ala Ile Gly Asp Gly Gly Asn Asp Val Ser Met Ile Gln Ala 820 825 830 gca gac tgt ggg att ggg att gag gga aag gag ggt aaa cag gcc tcg 2544 Ala Asp Cys Gly Ile Gly Ile Glu Gly Lys Glu Gly Lys Gln Ala Ser 835 840 845 ctg gcg gcc gac ttc tcc atc acg cag ttc cgg cac ata ggc agg ctg 2592 Leu Ala Ala Asp Phe Ser Ile Thr Gln Phe Arg His Ile Gly Arg Leu 850 855 860 ctc atg gtg cac ggg cgg aac agc tac aag agg tcg gcg gca ctc ggc 2640 Leu Met Val His Gly Arg Asn Ser Tyr Lys Arg Ser Ala Ala Leu Gly 865 870 875 880 cag ttc gtc atg cac agg ggc ctt atc atc tcc acc atg cag gct gtg 2688 Gln Phe Val Met His Arg Gly Leu Ile Ile Ser Thr Met Gln Ala Val 885 890 895 ttt tcc tca gtc ttc tac ttc gca tcc gtc cct ttg tat cag ggc ttc 2736 Phe Ser Ser Val Phe Tyr Phe Ala Ser Val Pro Leu Tyr Gln Gly Phe 900 905 910 ctc atg gtg ggg tat gcc acc ata tac acc atg ttc cca gtg ttc tcc 2784 Leu Met Val Gly Tyr Ala Thr Ile Tyr Thr Met Phe Pro Val Phe Ser 915 920 925 tta gtg ctg gac cag gac gtg aag cca gag atg gcg atg ctc tac ccg 2832 Leu Val Leu Asp Gln Asp Val Lys Pro Glu Met Ala Met Leu Tyr Pro 930 935 940 gag ctg tac aag gac ctc acc aag gga aga tcc ttg tcc ttc aaa acc 2880 Glu Leu Tyr Lys Asp Leu Thr Lys Gly Arg Ser Leu Ser Phe Lys Thr 945 950 955 960 ttc ctc atc tgg gtt tta ata agt att tac caa ggc ggc atc ctc atg 2928 Phe Leu Ile Trp Val Leu Ile Ser Ile Tyr Gln Gly Gly Ile Leu Met 965 970 975 tat ggg gcc ctg gtg ctc ttc gag tct gag ttc gtc cac gtg gtg gcc 2976 Tyr Gly Ala Leu Val Leu Phe Glu Ser Glu Phe Val His Val Val Ala 980 985 990 atc tcc ttc acc gca ctg atc ctg acc gag ctg ctg atg gtg gcg ctg 3024 Ile Ser Phe Thr Ala Leu Ile Leu Thr Glu Leu Leu Met Val Ala Leu 995 1000 1005 acc gtc cgc acg tgg cac tgg ctg atg gtg gtg gcc gag ttc ctc agc 3072 Thr Val Arg Thr Trp His Trp Leu Met Val Val Ala Glu Phe Leu Ser 1010 1015 1020 tta ggc tgc tac gtg tcc tca ctc gct ttt ctc aat gaa tat ttt gat 3120 Leu Gly Cys Tyr Val Ser Ser Leu Ala Phe Leu Asn Glu Tyr Phe Asp 1025 1030 1035 1040 gtt gcc ttt atc acc acc gtg acc ttc ctg tgg aaa gtg tcg gcg atc 3168 Val Ala Phe Ile Thr Thr Val Thr Phe Leu Trp Lys Val Ser Ala Ile 1045 1050 1055 acc gtg gtc agc tgc ctc ccg ctg tat gtc ctc aag tac ctg agg cgc 3216 Thr Val Val Ser Cys Leu Pro Leu Tyr Val Leu Lys Tyr Leu Arg Arg 1060 1065 1070 aag tct tct cct ccc agc tac tgc aag ctg gcc tcc taa 3255 Lys Ser Ser Pro Pro Ser Tyr Cys Lys Leu Ala Ser * 1075 1080 <210> SEQ ID NO 28 <211> LENGTH: 464 <212> TYPE: PRT <213> ORGANISM: Escherichia coli <400> SEQUENCE: 28 Met Pro Asp Ala Lys Lys Gln Gly Arg Ser Asn Lys Ala Met Thr Phe 1 5 10 15 Phe Val Cys Phe Leu Ala Ala Leu Ala Gly Leu Leu Phe Gly Leu Asp 20 25 30 Ile Gly Val Ile Ala Gly Ala Leu Pro Phe Ile Ala Asp Glu Phe Gln 35 40 45 Ile Thr Ser His Thr Gln Glu Trp Val Val Ser Ser Met Met Phe Gly 50 55 60 Ala Ala Val Gly Ala Val Gly Ser Gly Trp Leu Ser Phe Lys Leu Gly 65 70 75 80 Arg Lys Lys Ser Leu Met Ile Gly Ala Ile Leu Phe Val Ala Gly Ser 85 90 95 Leu Phe Ser Ala Ala Ala Pro Asn Val Glu Val Leu Ile Leu Ser Arg 100 105 110 Val Leu Leu Gly Leu Ala Val Gly Val Ala Ser Tyr Thr Ala Pro Leu 115 120 125 Tyr Leu Ser Glu Ile Ala Pro Glu Lys Ile Arg Gly Ser Met Ile Ser 130 135 140 Met Tyr Gln Leu Met Ile Thr Ile Gly Ile Leu Gly Ala Tyr Leu Ser 145 150 155 160 Asp Thr Ala Phe Ser Tyr Thr Gly Ala Trp Arg Trp Met Leu Gly Val 165 170 175 Ile Ile Ile Pro Ala Ile Leu Leu Leu Ile Gly Val Phe Phe Leu Pro 180 185 190 Asp Ser Pro Arg Trp Phe Ala Ala Lys Arg Arg Phe Val Asp Ala Glu 195 200 205 Arg Val Leu Leu Arg Leu Arg Asp Thr Ser Ala Glu Ala Lys Arg Glu 210 215 220 Leu Asp Glu Ile Arg Glu Ser Leu Gln Val Lys Gln Ser Gly Trp Ala 225 230 235 240 Leu Phe Lys Glu Asn Ser Asn Phe Arg Arg Ala Val Phe Leu Gly Val 245 250 255 Leu Leu Gln Val Met Gln Gln Phe Thr Gly Met Asn Val Ile Met Tyr 260 265 270 Tyr Ala Pro Lys Ile Phe Glu Leu Ala Gly Tyr Thr Asn Thr Thr Glu 275 280 285 Gln Met Trp Gly Thr Val Ile Val Gly Leu Thr Asn Val Leu Ala Thr 290 295 300 Phe Ile Ala Ile Gly Leu Val Asp Arg Trp Gly Arg Lys Pro Thr Leu 305 310 315 320 Thr Leu Gly Phe Leu Val Met Ala Ala Gly Met Gly Val Leu Gly Thr 325 330 335 Met Met His Ile Gly Ile His Ser Pro Ser Ala Gln Tyr Phe Ala Ile 340 345 350 Ala Met Leu Leu Met Phe Ile Val Gly Phe Ala Met Ser Ala Gly Pro 355 360 365 Leu Ile Trp Val Leu Cys Ser Glu Ile Gln Pro Leu Lys Gly Arg Asp 370 375 380 Phe Gly Ile Thr Cys Ser Thr Ala Thr Asn Trp Ile Ala Asn Met Ile 385 390 395 400 Val Gly Ala Thr Phe Leu Thr Met Leu Asn Thr Leu Gly Asn Ala Asn 405 410 415 Thr Phe Trp Val Tyr Ala Ala Leu Asn Val Leu Phe Ile Leu Leu Thr 420 425 430 Leu Trp Leu Val Pro Glu Thr Lys His Val Ser Leu Glu His Ile Glu 435 440 445 Arg Asn Leu Met Lys Gly Arg Lys Leu Arg Glu Ile Gly Ala His Asp 450 455 460 <210> SEQ ID NO 29 <211> LENGTH: 472 <212> TYPE: PRT <213> ORGANISM: Escherichia coli <400> SEQUENCE: 29 Met Val Thr Ile Asn Thr Glu Ser Ala Leu Thr Pro Arg Ser Leu Arg 1 5 10 15 Asp Thr Arg Arg Met Asn Met Phe Val Ser Val Ala Ala Ala Val Ala 20 25 30 Gly Leu Leu Phe Gly Leu Asp Ile Gly Val Ile Ala Gly Ala Leu Pro 35 40 45 Phe Ile Thr Asp His Phe Val Leu Thr Ser Arg Leu Gln Glu Trp Val 50 55 60 Val Ser Ser Met Met Leu Gly Ala Ala Ile Gly Ala Leu Phe Asn Gly 65 70 75 80 Trp Leu Ser Phe Arg Leu Gly Arg Lys Tyr Ser Leu Met Ala Gly Ala 85 90 95 Ile Leu Phe Val Leu Gly Ser Ile Gly Ser Ala Phe Ala Thr Ser Val 100 105 110 Glu Met Leu Ile Ala Ala Arg Val Val Leu Gly Ile Ala Val Gly Ile 115 120 125 Ala Ser Tyr Thr Ala Pro Leu Tyr Leu Ser Glu Met Ala Ser Glu Asn 130 135 140 Val Arg Gly Lys Met Ile Ser Met Tyr Gln Leu Met Val Thr Leu Gly 145 150 155 160 Ile Val Leu Ala Phe Leu Ser Asp Thr Ala Phe Ser Tyr Ser Gly Asn 165 170 175 Trp Arg Ala Met Leu Gly Val Leu Ala Leu Pro Ala Val Leu Leu Ile 180 185 190 Ile Leu Val Val Phe Leu Pro Asn Ser Pro Arg Trp Leu Ala Glu Lys 195 200 205 Gly Arg His Ile Glu Ala Glu Glu Val Leu Arg Met Leu Arg Asp Thr 210 215 220 Ser Glu Lys Ala Arg Glu Glu Leu Asn Glu Ile Arg Glu Ser Leu Lys 225 230 235 240 Leu Lys Gln Gly Gly Trp Ala Leu Phe Lys Ile Asn Arg Asn Val Arg 245 250 255 Arg Ala Val Phe Leu Gly Met Leu Leu Gln Ala Met Gln Gln Phe Thr 260 265 270 Gly Met Asn Ile Ile Met Tyr Tyr Ala Pro Arg Ile Phe Lys Met Ala 275 280 285 Gly Phe Thr Thr Thr Glu Gln Gln Met Ile Ala Thr Leu Val Val Gly 290 295 300 Leu Thr Phe Met Phe Ala Thr Phe Ile Ala Val Phe Thr Val Asp Lys 305 310 315 320 Ala Gly Arg Lys Pro Ala Leu Lys Ile Gly Phe Ser Val Met Ala Leu 325 330 335 Gly Thr Leu Val Leu Gly Tyr Cys Leu Met Gln Phe Asp Asn Gly Thr 340 345 350 Ala Ser Ser Gly Leu Ser Trp Leu Ser Val Gly Met Thr Met Met Cys 355 360 365 Ile Ala Gly Tyr Ala Met Ser Ala Ala Pro Val Val Trp Ile Leu Cys 370 375 380 Ser Glu Ile Gln Pro Leu Lys Cys Arg Asp Phe Gly Ile Thr Cys Ser 385 390 395 400 Thr Thr Thr Asn Trp Val Ser Asn Met Ile Ile Gly Ala Thr Phe Leu 405 410 415 Thr Leu Leu Asp Ser Ile Gly Ala Ala Gly Thr Phe Trp Leu Tyr Thr 420 425 430 Ala Leu Asn Ile Ala Phe Val Gly Ile Thr Phe Trp Leu Ile Pro Glu 435 440 445 Thr Lys Asn Val Thr Leu Glu His Ile Glu Arg Lys Leu Met Ala Gly 450 455 460 Glu Lys Leu Arg Asn Ile Gly Val 465 470 <210> SEQ ID NO 30 <211> LENGTH: 526 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 30 Met Thr Ser Asp His Glu His Met Thr Ala Val Cys Ala Ser His Val 1 5 10 15 Gln Thr His Gly Ser Gln Leu Gln Ile Gln Lys Leu Ser Pro Cys Phe 20 25 30 Arg Pro Pro Thr Pro Ala Phe Arg Ile Ser Ser Ser Ile Ile Leu Leu 35 40 45 Gly Ala Gly Leu Ala Gly Pro Ser Thr Gly Asp Arg Trp Phe Gly Val 50 55 60 Ser Val Val Gly Thr Gly Leu Phe Leu Pro Pro Leu Gln Leu Leu Leu 65 70 75 80 Pro Pro Arg Leu Leu Phe Thr His Ala Ile Leu Glu Arg Leu His Leu 85 90 95 Trp Leu Ala Leu Pro Pro Val Leu Val Leu Gly His Ala Leu Leu His 100 105 110 Cys Lys Val Gly Gly Ser Thr Ala Arg Ala Gly Asp Gln Leu Val Gln 115 120 125 Arg Val Leu Leu Leu Ile Val Phe Leu His Arg Trp Val Gln Val Trp 130 135 140 Pro Glx Gly Thr Glu Val Asp Ile Leu Gly Met Gly Ser Arg Thr Gly 145 150 155 160 Gly Arg Arg Gly Pro Glu Leu Arg Pro Gly Phe Arg Ile Ser Ile Leu 165 170 175 Ser Ala Tyr Ile Ser Asn Tyr Ala Phe Ala Asn Val Phe His Gly Trp 180 185 190 Lys Tyr Met Phe Gly Leu Val Ile Pro Leu Gly Val Leu Gln Ala Ile 195 200 205 Ala Met Tyr Phe Leu Pro Pro Ser Pro Arg Phe Leu Val Met Lys Gly 210 215 220 Gln Glu Gly Ala Ala Ser Lys Val Leu Gly Arg Leu Arg Ala Leu Ser 225 230 235 240 Asp Thr Thr Glu Glu Leu Thr Val Ile Lys Ser Ser Leu Lys Asp Glu 245 250 255 Tyr Gln Tyr Ser Phe Trp Asp Leu Phe Arg Ser Lys Asp Asn Met Arg 260 265 270 Thr Arg Ile Met Ile Gly Leu Thr Leu Val Phe Phe Val Gln Ile Thr 275 280 285 Gly Gln Pro Asn Ile Leu Phe Tyr Ala Ser Thr Val Leu Lys Ser Val 290 295 300 Gly Phe Gln Ser Asn Glu Ala Ala Ser Leu Ala Ser Thr Gly Val Gly 305 310 315 320 Val Val Lys Val Ile Ser Thr Ile Pro Ala Thr Leu Leu Val Asp His 325 330 335 Val Gly Ser Lys Thr Phe Leu Cys Ile Gly Leu Leu Asn Ala Gly Leu 340 345 350 Ser His Thr Glu Tyr Gln Ile Val Thr Asp Pro Gly Asp Val Pro Ala 355 360 365 Phe Leu Lys Trp Leu Ser Leu Ala Ser Leu Leu Val Tyr Val Ala Ala 370 375 380 Phe Ser Ile Gly Leu Gly Pro Met Pro Trp Leu Val Leu Ser Glu Ile 385 390 395 400 Phe Pro Gly Gly Ile Arg Gly Arg Ala Met Ala Leu Thr Ser Ser Met 405 410 415 Asn Trp Gly Ile Asn Leu Leu Ile Ser Leu Thr Phe Leu Thr Val Asn 420 425 430 Leu Ile Gly Leu Pro Trp Val Cys Phe Ile Tyr Thr Ile Met Ser Leu 435 440 445 Ala Ser Leu Leu Phe Val Val Met Phe Ile Pro Glu Thr Lys Gly Cys 450 455 460 Ser Leu Glu Gln Ile Ser Met Glu Leu Ala Lys Val Asn Tyr Val Lys 465 470 475 480 Asn Asn Ile Cys Phe Met Ser His His Gln Glu Glu Leu Val Pro Lys 485 490 495 Gln Pro Gln Lys Arg Lys Pro Gln Glu Gln Leu Leu Glu Cys Asn Lys 500 505 510 Leu Cys Gly Arg Gly Gln Ser Arg Gln Leu Ser Pro Glu Thr 515 520 525 <210> SEQ ID NO 31 <211> LENGTH: 25002 <212> TYPE: DNA <213> ORGANISM: Caenorhabditis elegans <400> SEQUENCE: 31 accctgcaat aggatatcat tacgatgtaa gtattcaata tttatttcaa atttgtattt 60 tgttgacaaa ttttcaaata atgaaatgtg aatgcttcat gaattcttaa gctttcgggg 120 cacagaaagt gagggcgatc ttcattttaa ctgcaaaatt tcaggtacca tcatgtaatg 180 gttgtaaaac atttttccgt cgaacaatta tcacgggaag aaaattcaca tgtgctaaac 240 aaaagaaatg tatggatgga acagaaccag ttggtaagtt tcttttaatt ttaagggtaa 300 tgtcttattt tttcagatat gtcgaagcgt ctttgccgag cttgtcgctt tgcaaaatgt 360 gtggaagttg gaatgaatcc aatggcaatt caagcagaag ttaaaactga tgaaggcaaa 420 gttttaagaa gtgaagtatt gaatcaaaga gaatcgctag gggttgtttc atctgtaagt 480 tgtttttttt ttaaaataca tctattaaat ttcagttgat agtaaccgag gaagatttgt 540 taagcagaat gattgaaaaa ttaacatttg tggaaagtaa ggttgaacca ttacatcgtt 600 ctggaatgcc tcctggttac agagtaagtt aatgattttt ttttaatttg caagaacttt 660 aattgatttc aggacataag aaaattggaa gaaattcttg attcaaaacc agtacttgtt 720 gttacggata ttcccaattt gaaattctgc ccttcaccat gtgcgaatga aaaaaggtga 780 gttttttatt aaaatgagat tgaaaatttt cccacttctt tagaccaaga cgacatttca 840 ccaactacgt tcacacaagt tacctggctt ctcttgaatc ttcaaaaatg tttgaatttt 900 cttcacaact tgatttggaa tccagaattc ttttaatgaa acacgcgaca ctaatttgtt 960 cgaatatgat gaatgcattc ttttcgatta acgaaatgaa atcagatatt cttaggcatc 1020 cggatgggag catgtcagga catatgagaa aattcgatcg agagaatgat gtcatgacag 1080 atcatgtcaa attgatacag aagacattga tcactttcct aaatcataaa gtcgacaaaa 1140 ttgaatatct tttattcaaa gctattatgc tttgcaatcc aggtattttc cttgccgtca 1200 tatatataat ttaaacgatt acttgaaatt tcagctgtgc ccggattaga ttcctggaac 1260 caagaaatca tcgaaaagga acgaaatcaa tacgttaaag ctcttctaaa ttattgtctc 1320 cttcaacatg gaaaacttca aggcccaaca agattcgcaa ctattctcgc aatggctcca 1380 attatagaga atcaatcgaa aaatcaaaaa gatttccatg tgtacattaa agcaaagcat 1440 ttccagaagc acaaaaagat gggaacaacg ttcagaaaat gtatcagttg catgtttgat 1500 caaattatgg aaacataaat aatcaatgta aataaatgac aatgtttttg tttaactgtt 1560 aatataatct gttcatcctc tgtataatat tctacctcaa aatacaaaaa taaacatctc 1620 ataatttatt cccctaattc aaactacaaa gcatgatgga aactctatac attagtcgtt 1680 tgtcgtttct tgtggacgtt tcatgtggtg ctgaagttag gaatttgggc gatttaccta 1740 cttgatgtaa cttctaagtt taacctgaca tttgcaattt taagaatttt ccaagcatta 1800 taaaaaaaat agttcacact tttcatgtgc gagtagatga taattatgca agttcaatct 1860 tgcacaggat taaacctact agttcacttc tgatttttat atattaactt atcaatgtct 1920 tatttttgaa gatttttcgt gtgacagagg tttcaaaaaa aagagatatt caatcagaat 1980 tctaaaagac aggttgtgaa acttcaatat tttcgaatat accgcacttg tagtgaattc 2040 agaatataat tttcaattta aaaaacacaa tttttgaagg tacgcaccaa tcacgcatct 2100 gaaaatttaa gaaactacac atatatcagc aattgatctt caaaattata acgacaaaac 2160 tgaacttcaa actttcaaaa attccagaaa ttaaaacgac tgaagtgatt cttgcagagt 2220 gttgactcaa agtgaccaat tggagaccat acttgttaat tctttcaaaa acattttgat 2280 cgtcgcctgt tacgtataca aaagaagagt actgattcat caaatttgga atataatccc 2340 acccacatgt aagtgtcgat agttgttgaa tcggctgaaa actttttccg aaacagaaag 2400 gagaaagaac aaacatttga tagaggcgat agtcacatca ttttccactc tttttctcta 2460 ccatcctatc tctaatcagt ctagtcttca ctaaatcaac cgtttttata ttccataaat 2520 tgatccatta atgtcttcga aggataggta gatatattta tcttgcgttt attttatttt 2580 tccataatat tccagtgatt ctccaccaga aacttttgaa gtgtgcatct cctcaccaga 2640 aatacacaaa aaagaaataa tgactccacc acagaaatca aaaccaaaaa gaaatcgacg 2700 gaaaatttac aaaattcttc cacaaaatca atgtccatcg gtgtgtcaaa tttgtagaaa 2760 tccagcaatt ggatatcatt atgaggtaaa ctacagtata gtttgtttta ttgttagaag 2820 tagtgtaaag gttcactaga gctactttaa agattacgat tcgatgagtt attcgattta 2880 ctacatgaac gctaaactga gaatatgact ttaaaaaatg ttcaactttt cggttttgag 2940 aaaaatcaaa aggcggacac gaaacacgat tccacaattt aagttttcaa tactattctg 3000 ccttggaaaa tttatttggt agaaaagtct acatacaaac ccaaaaatca gtataaaaat 3060 taagcactct aaaagagtct cacgttttag gtaccatctt gcaatggatg caaaacattc 3120 ttccgtcgta caattatcac tggccgtaaa tttaaatgtt tcaaagttag taattgtctt 3180 gatggtaatg acgtaatcgg tgagttcaat aagagtctta atgaaatttt tttttgatat 3240 ttgcgttttt gatttctgcc ttttgatcgg aaacacattt ccattcaaat tttacacaca 3300 ttttccagat acatcgaagc gtgtttgtcg agcatgtcga tttgaaaaat gtgtacaagc 3360 gggaatgaat ccaatggcaa ttcaagcaga agcaaagact gatgaaggag aagaacttaa 3420 gaaattgatc gctaaaaagt ttgaaaacgg agaaaaatta aatgatggaa ccgtattttt 3480 taatgtacat gacagattga atcaaatact tggaaagttg ataaaaattg aaacaaaatt 3540 ggaaaaagtt catgataatg gaatgccaat gggatttttg gatcaaagag atttaagcac 3600 tgcgctctct tcaaaagtta tctataacaa tatggaaata ccgtcaatga gctatactcc 3660 tgttaaaatt tcaaaaaaca ccggattgtg agtttttttc aaaagaaaat tccaaaaatt 3720 tcaaaaaatt ctgaagtaat gtttaaatcg ttttatgagc attgaagctt gcctgattgg 3780 ccaaaaataa acaaaaagct ccaggcaact gtaaaaataa ataaataaag attataattg 3840 acaaacagta tttttacaaa ttgttgaaaa ataagttctg tgcgttttca ggccaaaacg 3900 aaggagtcga aactttgttc attcaagttg tcttgcatct atcgaatatt ccaaaacatt 3960 tgacttttca agtgcaattg acatttcaag taaagtacgt ttttggaaca gattttatct 4020 gaacaatgac cttattcgat tatcttttga gattatagac tagcaccatt tttgcaagta 4080 ttcaaaatta atattagact tatttcagat aattctcctt aaaaatactg cactatcttg 4140 tgcaaacttg acaaatgctt atacaacatt cagaaagctg aaatcagata cacttttata 4200 cccagatggt agtatttatg ggccaccacg acggaaaaat ggtcctttga ttgaaaaaca 4260 acgatcattt ttacaaaata cgttgatatc atttatgact aacaatgttg ataaaactga 4320 atatatttta ctaaaagcaa tagtactatg taatccaggt atgtcataag taccaaataa 4380 ttaattttca aataaatatt acagcaataa tcgatctacc ttatgccgat tcaaaacata 4440 ttcaaagaga gcgagaggtt tacgctcagt gtttgttccg atattgtcta ctacaacatg 4500 gtacattaca cgggcctgca aggttttctg ctttattatc aatattcaat gtgttggaaa 4560 atcaacagaa ggaacaaaag gattactatt tatacatcaa acttatacat agtcaaaaac 4620 acaaggatcc tgaggtttta aagaagaaat gtattagtgt aatttatgat cagattatgg 4680 attagaaaaa gaaatctaat atgatagtga ataaatagat tgatgaataa aaataatttt 4740 gaaatgtaca tgtttacatt tttatttgag tacaatttgt ttcttgaaac catattaacc 4800 atgaagtcca tcaattttat cttacaaaat aaaccactcc gacttgaaaa ttaagtgtgg 4860 aatttgccag tacttcagct tcctttaaaa aaaaattcaa aatgtttaat tcttttccca 4920 attttctatg cggtatttca gaacttcaaa ctattgggaa cattttgaga caacccccac 4980 agcttaaaag ttttcaaaat tgtttctccg ataaaatgca catataccta acttttgaat 5040 ataacccatt ttctctctga gttttatcgt gatttctgtg acgaaacact gaatgcgtac 5100 tgcttttatc ccgatttttc attgatctcc attaaaaaca tcacagtttt gttgttatta 5160 tctggtttac aaagagtcat attcagctgt acatacaagg gatctaatcg caacacatta 5220 tgtgcacacg agctttgtat cgcaaacaat acatcgcggc taaaaatttt cgttttctct 5280 actttctcat tcatttatac ttcatgcaac gtgtgtagat gagggaagtc agacgcagac 5340 ggtacgtaga ctccaaagaa acaaagatgc gttgatcggt gcagacgcca gtcctctctc 5400 taccgttcta tggtttctgc gattttatta ttccaccttt tgtgaagttc gatcacttta 5460 cttttcttgc ttcaatatca gaaagatgct tcctgacttt attacagtac catcaacaag 5520 tgaaaagtat gtttaatctc cagaattgtt ttgtttgcat agatgatggg aaatcaataa 5580 ccttctgttc atgtgacgcg cggtatcata tttctcttct tttttcagat gtctttctcc 5640 ggaattgttg ctaccaaata tggatgagaa cttggaagat tcaaaaccaa gcgtgagttt 5700 ttcctattcg gaaaaatata ctttctaaaa aaatatttaa aaacaatcaa aaagttaaag 5760 tattaattat atatctcaaa acgatatatc tcaaaaacgt tatattcgaa tttcagtctt 5820 taaaatatca aaaggcgatg atgagccgag gaacatgtcc atcaaattgt aaagtctgta 5880 ggcactcagc tactggatat cactatgatg ttccatcttg taatggatgc aaaacatttt 5940 ttcgacgatc aattctggat ggaagaaaat atacatgcct gaagatgaga aaatgtttga 6000 gtggaactga acctgttggt atgctttaat tttctcacta attcaagatt tcactatccc 6060 tatcatatac ttcaaaccat ttcagacttg tctaggcgca tgtgtcgagc atgccgattt 6120 gagaaatgtg tagaagctgg aatgaatcca tctgcaatac aagccgacat gaaaaccact 6180 gacggtgagc tgttgagaaa agaaattatg ataaagcaga agacagccgt tgattttttg 6240 aatactccac aggtatatta caaaaataat tgcaacaatg ataatcactg attatttcag 6300 gttattatga gttttgaaga taaagtgcaa ggaataattg gcaagctgac agtaatggaa 6360 ttgaagatag aaccattgta tacaggagga ttgcctccag gcaatagagt atgatgcttt 6420 tcctgtaaac tggtaacttt ataattcagg atatcaggaa attggacgag ttgattgatg 6480 ctccactgat tctcagctat gacgaaattc caaatttaaa gtattgtccg agtgtagacg 6540 aattgaccgg agagtgagtt tttattcaga aaaatcaatg attccataaa attatttttc 6600 agaataaagc ccagtggagc ttgctacata cattgcggct acctagctag tatagaatat 6660 tcaaaaatgt ttgactttgc tcataaaata gatgttgcta gcaaagcaac tctgataaaa 6720 catgcaacaa ttatgtgcgc agatatcatg acagctttct tctcttacta tcaacgtaaa 6780 tccgatcgac tgattcatcc aaatggaatg tttgcaggac caccaaaata caggtgaaac 6840 acttcagtaa atatgttttt gaaaaatgat tttgcttgag atatggtgaa gccggtacaa 6900 aatatcaagc ttcaatgcaa agaactctgg caacagtgct ccgacatgaa cttaatcgaa 6960 ttgaatatat gctactcaaa gctattgtgc tttgcaatcc aggtatgacc aaaaattttg 7020 aatcaaaaac acaaaaacat caatttcaat acaggagtcc atgaaaataa tatcttttaa 7080 taacacgatt tgatttccag cagtctctag tctttctatt tcggtacaac aaataattgg 7140 aaaagaacgt gaagaatatg ttcgaactct acttacatac tgtcttctca attatggttc 7200 tgttcatgga ccatcaagat tttctgccct tcttgctatt atgtcagttc ttgaaagtca 7260 acagaagaat gcaaaggact ttcatttatt ggctaaagcg acaatactga aagatgcagt 7320 tagatacaca cgaattagca atctttacga acaaatcatg gagtcgtaaa gattagaaat 7380 tgttgaaatt aggatatttg ggtactcgaa gtctttattt ttattacttt caatttatgt 7440 tatatttcta tttatatata catttgagaa atacaaagaa atcagagaaa atcatcagaa 7500 ttgttgcatt ggttctagcg ggtattgtaa ataaaatgtt atttttccgt ttcgaatctt 7560 ctctacataa agcttttcga tcagcacata aagtgagaat agaagtttgg attaaattac 7620 aacctgaatc cgttatccgc aatcagttta accgcatcgt aaagacaatc agcagtgaga 7680 tcaggagtca cgggcatctt ttcgaaatct ggtctccatt taccagttct cacttgaaca 7740 cctcgcattc cacaagcttg agcaccgcct acgtccgaca tcaaatcgtc gccaaccatt 7800 acaatctgga aattagaaaa tgaagtcaca aagattttgt tccaacataa gaatggaaat 7860 tgaaattccg atgtataatt gttttactta cttcttctgg tttcataccc aatgcattca 7920 ttccttgctc gaaatagaac cggcttggtt ttccaatgtt caaaacctca caattagttg 7980 agaacttgag agcagcagca aaagcgccga catcaatgca cggaccatca actcgttgga 8040 agaactttct aaaatagaaa agggaaatgt gttagagaga acaggaaaca attattaccc 8100 attgcccatt gttatgagaa gcggtttagg catgtcgatg agaattcgga aagctctgtt 8160 gattcgatcg aatgagaaac cttcttcaac ttcacccatc acaacacaat tcggagatga 8220 ggtgtcgatt ccatcgaagt attcaagcac atcttgagag gaaaaagaac tgattgttgt 8280 cagagaatta aagaatcaaa taccgtctct gacaaacaga tgtgggcgaa gcttgttctc 8340 tcgacaatat tgtgcaacca ctggagctgg agttatgacg tcttcctctc gaacactgaa 8400 aataaaaact attataattc caataagtag tgggtgattt gaaagctgcc tatttgacat 8460 tattaatttt tacattattc ggtaacactt tttttctaaa tttgttctat cagacttcag 8520 taggacattt tggtggtttt tgaattgatg actgatcaac agaaatattt tctgaatctc 8580 aaaaaatcaa tggctgggag agtgaaattt tttttctgat ttcttccatc ggaaaacatg 8640 caaaaattgg gtaaaatttg atttctacaa aaaccgtgaa ataactctca aacttacttg 8700 attccgagtc tttgaagtct ccgagcaaca tttctgtttg aatttccttt tgcattgcta 8760 agaaatttta ccttcgagtg ttgatacaaa ctgtaaatat tttcaatatt atgtatctat 8820 ttttgcattt tacaatattt ttcttatcta atgcaccgtt gttctaggtg cacatgcacg 8880 caaatgttta ccttgagggc attttttata aacagttttc caaaaatttg tggaaatttt 8940 ttcggattga gaacaaaata caggacatgt aaaacgattt gacataaaag tgataaactt 9000 gaaaaatgag gatacatgat ttgtatctac catttttatt aacaaaaaag agttgaagtt 9060 tttattagct agaaaaatca ttaaaaaact tacaaattaa ccgcttcagc tgattttgga 9120 acagcaactc catcggattt ataaatacta ttatacaaaa ctcccgttat atcgagcagg 9180 aacccattaa ccgctcttcc atttgacatt cttcgaccct aaagtttcaa tatgaaattt 9240 cataatcctg aaaccaagac caaagttcag gaaaccagca aaagctataa catagaacaa 9300 aaacagaaaa gatagaatga aaatcttgag atagctatgg aaaaggaaga gaggaaaggg 9360 tctttctctc tttctttcca tgcgggggca atatgggcag aaagggtccg tttagatgtt 9420 cttctctctg ctcactgcat gtgcacccag tacgtcttct tcacttctct caccctcttc 9480 actcctttct tgttccacta tctcttcaat acacatgtcc agctgcctat tggaccttct 9540 gttttcaagg tgttgtcaca acttttgagc tatgaaacta ctttgatgct aattagatat 9600 gatttagtaa tatgtatttt gtttcatagc tcacacagaa aatgtatatc atgagaaaca 9660 tcagagagat ttagcaatgg atccgtaatg tatctttaat gaactcaaga tattcatatt 9720 ttaaaacgtg tttacactca aaataaatga atattgtaag aaaacactga atcgcatacc 9780 caaaagcctc caaactttca aaagatgtag agtaaccata caaaacaata ggaagagttc 9840 gaaatgtgca gtcacgcgcg catttcttgt gtctctaagg tgtgaattac gcaaacacag 9900 agacggcaga ttgcggtatg tcggtcgaga atgatgaatt acgatcaaga caagaaaaga 9960 agaagaagaa ggaaagacga accagagatt ttcgactgca gtagctgagg aacaattgta 10020 gaagaatact cggcgtcact ttataaataa atgaaacaaa atcttgatta aaagagaagc 10080 tagaaggtca cgttaatact atgaggttat gcacttgaaa ttatgcaata tttcaaatgg 10140 cacagaaaaa accaacaggt aataaaatca atcaagtctg aaaatgttgc tctagaaatg 10200 tgtatcgtac aatgaagcgt gtatctctga atcaaaaacg tttagactgt gacaattctt 10260 tccggaatcc aataagaaca aagtgtggaa aagggatgca ccgagctgaa aatttattga 10320 actgtagttt gaggaactca atcaagacga accaaacatc attcatgcga agaaacatca 10380 tttaatttta gaaactataa aaaaaaggtt aaaacattta actggcattc agagacaatt 10440 cttaaaactt tgatggcgca aaacaacaag acgtcatcca cagaagaaac tgtgccctac 10500 atcttcaaat agatcggaca tcatctatct acaagtattc tttctttttc attctcttgt 10560 ccctctccat cagccctcct tgatagtctt ttttcacatt ctcaccttct tttttgctgt 10620 ctatttactt ttatgattgc cgcaccaata aatatctcta ctcactttca aactccttat 10680 cgatttaatc catatgtact atacttttaa agacagatta tgcgtgaggc gaatgtgaca 10740 tagtctagaa ttccggaaat tgtgcgcaaa attcttagaa acatatgtag ttgagtcgca 10800 tttttcgaat ccagttttta tttcagcggc tgttttattt cagcggctgt tttatgactg 10860 catttttaca agctgctaat tgcgaatttc cacgataacg gtttggttgg cacgtgtttc 10920 ccaataaatt tgtaagcatt ttacataatg caccaatttt tccctccaca catcatttcc 10980 gaatttgatt tttttttctt aaattacttg aacatattat cgaaaaaaat tgaaactgtt 11040 cccatatcta caaaacatca ttcaatagta ttagattcag aaaactgcct acaaattgat 11100 tttttaacca ttggttttca tgaactatct ttcaacaatt cagatgaact ttttttaaaa 11160 ttcaaagtgc tattatgtta ttacaattag aagaaattaa aaattcaaat tatacaattt 11220 aagtttggct ctatcacggg ttttaaatga atttcttgaa aacgcgcggc aaaagcttag 11280 caaactgtct attgaactta cccttactat taatcattga aattttcaaa tgcgtatatt 11340 taaaaaaaca gaacggtatg gattctcatg ataagacagt tccttaatat ctcgtagcaa 11400 aaaaatcgac ccatctcttt gccccttgct tcatttctgc cgctttcttc gtgccaggaa 11460 ggtaggcatt ctcgtgaacc gacggtctga gtttgagtgt tttcctctta aaatgttcga 11520 ttattatagg tcgccagaca taaatattat ttgttaatat ttcatggtgt cgaaaccaca 11580 atcttttttc tttctacagg tggtttaata ttcgtttcct ttgtaaattt tcccatcggc 11640 aggaattggc ataacctgat tttttacagt agaaacacat atctagaaga ttaagatctt 11700 caattgtcca tctcgtttta aactgtcatt tctccggttc tttttggttt ttggtggcct 11760 tttaccggtt ttgttacgtt ttcccgaaat gatataaatt tttgagcttg tcacttaatt 11820 tatcaagcgg cgaccaaaga caaatacaca ccgcagaaga aaagtttgta aagagaaatg 11880 gaagttgact atatgtacat atataaaatg gaatgaatag tcgcatcaca ttgacggtga 11940 aagtacatgc ggtgatgcct tcgaggacat acggacacac tttccttctc caatttcatc 12000 gattaatttg tattgttata ttctgaattc caggttttca agacgaacat tgtgaatcat 12060 tttcatcaca ttgttctggt acaaataaaa tgtatttcca agttttcccg cacatttaca 12120 tttttgcttc actacgtgtt tagcacgtta tgcgataaga ggagaagtgg ctgtaaaatg 12180 gtttcgcact cccttttttc tctcccacaa tcattgcacg gtttctatga ccttttcgaa 12240 ctacattcct tcttttttca tttggaggtt tgatactgat atagtttgta gggtacccgc 12300 ttattgtaac tctaactgtt atatccattg tcattgattc atttatctgg ggggtattcc 12360 cttctatttg gcgaagtcta catttctcgt aaactgtaca aaataacgtt taaaagttct 12420 ttgaatactg aaaataataa aacggtttga acaatccaac ttattttcca attttcaaaa 12480 actagccgat catttttgtg aaataaaact attttctgct tagtatcgaa taaaacatct 12540 taacggtaaa aatgagtttt ttaaaacact tcttttaaac cttttttgga tttatttgaa 12600 ttttggcttt gaaatagtct ttattccgga aatttcatat aatctcaagg gcaaatacat 12660 tttgaaccgt gttcaaagtt atttaaaaat gcatttcgtt tgaatcactg agatttccaa 12720 aaattcaatg agtcataata catggagcaa caaatctata agaatgtcca cttgcttttg 12780 ttgttctttt gttttcaaac gttttggata taggctgtta ttttggccga caacaacttc 12840 agaatgtatt ttatgtttga gttttaaatg tgttactgaa aacaaataaa atgacagatt 12900 aatatatctc ttggtaaaaa ttaattaatt ttgttactac tttctgttcc tgaaaagcct 12960 gaaaaatcag accatttttt gcagtgtctt tgttaatgat aaaaaccgac atgcacactg 13020 accatcaaac cgattattat gaattaataa tttaatccga cagtttcctg tttctgttca 13080 tttcatctca cgaatgcttc aattttcatt ttttttttcc gtgtctctta atacgtttaa 13140 tttattacga gttcaagtaa caacgtttca atgaactctc atttagtttg aaaattaaaa 13200 tatttaagtt ctaacatttt gaagagtgaa cgatggtgag aaacaaagtg gcaccagttg 13260 aagatggagc caatattcaa agaaacttcg agcctccgcc accatataca actccaacgg 13320 attcacctga agacaagatt cgatcaaatt caactgcaac aaccgcatct caaccagaat 13380 ttcaaggatg ttggactatt gttgtagttg ccattttatt catcatcaat cttctcaatt 13440 atatggatcg gtatacgatt gcaggttagt tgacagtaac tattttacct ccttggtaca 13500 atattcaaaa cacaattcat gtaaccatgt gacagttttc cgtgcaataa aatttagtag 13560 agcctccaaa actataaaca acaaaaggta gaaagatgaa aatggccgga aaacgacatg 13620 agagagtatc ttgtttgaac ttgtcatcat tagaagataa gaatttacgt aatgggtgag 13680 tacaataact atgggacaaa catcattttt tgatctaaac ggagcattaa aaaatatgtg 13740 catgtcaaat ttgaattagt atgtgtggaa cttttcctac tgcaataata taacgttttc 13800 aacaaaaaaa acattaaaaa cattattcgt agaggaaatt agcatttaaa aaccaataaa 13860 atttttagga gtccttaatg atgtacaaac ctactacaat attagtgatg cttgggctgg 13920 actgattcaa acaacgttca tggtgttctt cattattttc tctccaattt gcggtttcct 13980 aggagatcgt tacaatcgaa aatggatttt tgttgttgga attgcgattt gggtgtctgc 14040 agtgtttgct tccactttta ttccatctaa tgtgagtttt tgactctaat catactattt 14100 cttcaatcaa cttcattttc agcaattctg gttgttcctt ttattccgcg gaattgttgg 14160 aatcggagaa gcatcttatg caattatctc cccaactgtt attgctgata tgttcactgg 14220 agtgctccgt tccagaatgc ttatggtctt ctactttgcg attccctttg gatgtggtct 14280 gggatttgta gttggatctg ctgtggctag ttggacagga cattggcaat ggggagtacg 14340 agtgactgga gttctcggaa tcgtttgtct cttgcttatt atcgtgtttg ttagagaacc 14400 agaacgtgga aaagctgaac gtgaaaaggg agaaattgct gcatctacag aagcaacaag 14460 ttatttggat gatatgaagg atttgctttc aaagtgagtt tctttcaatt ttatttaaaa 14520 agcaaccttt catatttcag tgcaacatat gtgacaagca gtctcggtta tactgcaact 14580 gttttcatgg tcggaactct cgcttggtgg gctccaatta caattcaata tgcagattct 14640 gctagaagga acggaacaat tacagaagat cagaaagcaa acattaactt ggtattcggt 14700 gcactcactt gtgttggtgg cgttcttggt gttgctattg gtacattggt ttcaaatgta 14760 aatattgtcg ttgaagatta gaaaaatata catctttttt ttagatgtgg tctcgtggag 14820 ttggtccttt taagcacatt caaacagttc gtgcagatgc tcttgtctgt gctatcggag 14880 cagcaatttg cattccaaca ctcattcttg ctattcaaaa cattgagagc aacatgaatt 14940 ttgcttgggt gtgtaaaatt tggactatga aacatttcaa attcgctttt ttttagggaa 15000 tgttatttat ttgcattgtc gccagtagtt ttaactgggc tacaaatgtc gatctgttac 15060 tggtaagttt cactcgatat tgaaacaaat tcccaaataa atgttttttg cagagtgtgg 15120 tagttcctca gagaagaagt tcagcctcat catggcaaat tttaatttct catatgtttg 15180 gagatgcttc tggtccttac attctgggat tgatatcaga tgcaatcaga ggcaatgaag 15240 atacggcaca ggctcattat aaatcattgg tcacctcatt ttggttgtgt gttggaactt 15300 tggtgttgtc agttattcta tttggaatat cagcaataac agttgtaaaa gataaagcca 15360 gattcaacga aattatgtgt aagtttcaga ctttttatag cttggcactg aatcaaaata 15420 ttcatttgca gtggcacaag ctaacaagga caacacatca agcgggacac ttccaattga 15480 agacagaaac acagaagacg aaactggttc cgaagttcaa catatgtaat tctaatattt 15540 tagtaaagct ggttgctcaa cccctcttcc cctacatatt acatttttct cacagtttat 15600 tgcgggtctg ctcttttttt tgtatttttg tatcccccat cagtcaatca ttcgcataaa 15660 ttttgcgttt ttattgccaa atcttttgta catttcggaa tattcgtgct gtcagagaaa 15720 atcaatgata gcagttaacg tgattcttta tgcttttcat agtgtttttg aaaaatatga 15780 aaacaagttt ctacttggaa cttttttatg gagcctcctt gttgtgtggc ggacaaatga 15840 caacagaagc tgggtaaaaa gtaagtttta ttcaaaacat actatacttc gccttcccac 15900 ctctcgcccg gaaatgtttt cggaaaagta tagtaaaggt cagttgaagt gttaacatgg 15960 taacaaaaat ggcatacaaa actaccggtc aggcgcgagg aggcgaataa agaggcgagc 16020 atgaatcacc aatgtggaac gccgttattt tggtttattg tagaaatatt actttcgaac 16080 aaaatcgtga cgccaaacaa aaataacttt tgcgttagct tgcagtttca atttttaaaa 16140 ttttccatgg ttgtccaaat ttctgcatag caaagtactt gtcacgtttt tcaacataag 16200 aacagttttc agaaaccaac tttgattcat ttttcattta cataatttca gatacaattg 16260 aaatctgcaa tattgtaaga ttcatatcag ttccattatt tcattcatct ccagttaatt 16320 ggctttattt atttactaca tcttcagcat tttcttttat tgctcaaagt tggtttctaa 16380 aaaatcaaaa gtttttaaac tgaccaattc agaaaaagaa tttactggat tcacattaat 16440 gatcgctctt catttgattc aatattttct catcacagga ttaagtgcaa tgacatattg 16500 gaatttagga aaacaattat ttaatttatt tgtttggcca gatgattctc gtcaactaat 16560 cattcagttg gcaatgattt tgtctactgc aactatgttc tgtcacgtat ttatcagtat 16620 ttggtcaaag ctttcagaga ttatcaatat aagtttgttt tttttacatt gtttctctga 16680 aacagtatta tatattttgc cttcagattg gtttctagtt tctaccatcg ttcatcctgc 16740 tattagtttc tacatctttc cgagatttca acatgttcat atgttgactg tttggttttc 16800 ttttcttatg atttcagtta aatttaatca gaagatgttc attaaagttc tcggagtctt 16860 tttcattgtt ctatactcca gccttttgga atcctgggaa ttatattttt tggatttgaa 16920 gtcacttttc aaaataaaat atttattcta acaagtgttt acgtagtaag cattaactta 16980 aatatggtga aatggaaaat atggtgctta aaaaacatca aaatgaacac agactaccga 17040 atttgataat gacacttcgg taatccttct caaaaatttt tattactgtt ttaaatgtta 17100 gaataaaagg ctcaaaaaca aacctccaac tattagcagc cggaagaagt aattaaattg 17160 aaacaaattt agggccgctg caagcctttt ctttataaat tttgaacaat tataaattca 17220 gtctttgaaa gccaatttga gttttattaa gcagtatata tttttagata gtcggcattt 17280 gaatctatca acaattttaa tcatcatcat catgtttatc atcaacagta cctccactgt 17340 ttcgtacaat atcatcatat cgtaaataag ttcttctgtc agcatttgat ggacctggac 17400 gaacacaatc cgcatatcga agacgatgaa atcttgtagc ataggttgga ggatctctga 17460 aattgttcca attttcttcc agtgttattc cgaaagaatc gtaccggtaa tgtaaaatcc 17520 atttctcaaa aattccttca aaacaagctt cagtgtcaga atttagaaga agtatctgaa 17580 tcaaacaaac ctaatcagat gaaactttaa acttcatacc caattaacac accaagattg 17640 gcttaaactg aatccaggcc accagaatag tcccatattg acaatatcgg attgtttaaa 17700 gaaaatcttg aaatgatcac gagatccttg ttcaaaatcg tttcttcctg ggttatcgag 17760 atgaaaagtt tcagaatcat gtccagattc atagaatact ttcaaatatg atgcggcgtc 17820 tgttccagca ccatctttgt cacaagtctc tatgactaca tcccagagac gaccgtcatc 17880 tacaaaactg aataattgcc acttatttga atttgaatac aacaattttc agaaaagttt 17940 tattatgatt gttgttcatt tcagcattgt atgcgtgatt ttaaacgatt ttcttgattg 18000 acacattagt tgaactcaaa gttaagatta aaaataatat taaactacat cattgttcac 18060 aacttcctgg aaagttttag tgaggttcat attcgaatat tctcttcaac cccattttta 18120 aaagttgact tgtgttttaa ttgtttaccc tttctgatca tttctatcat tgaaattgga 18180 agtcatttca cttttcttcc cacagctcat agttacaaaa acaagagtga ctgaaatttc 18240 aaaaactact tgtggtttca gtttttattt tattttatga atccagttag tcgaaaaaaa 18300 aacaatcaaa ttaattccat gcaacccaaa atattttaaa gttcttggta tttatgcagt 18360 ttttaaaact gagaatcaaa agttaaaata attgttttaa acttacgatg aacaacagtt 18420 tcattagttg gagaaaattg tgcaaaaacg atagtaacta gtaagcagta tattaaaaat 18480 gagtggaaca ttttggggag ttggtgaaaa aattatagga agagatgaaa gacactttgt 18540 gttctggaat cttctcctga cgacaactaa aaatccatca gcaattgaaa tgatcgattg 18600 atgattgatg gatgagtgtg atcatatgct tgctcaaaat actttcaaag cgaaaaaaaa 18660 acacaaggga aacatgagtt ctaaattttt gatcggaaca gatggtagaa attgaaatgt 18720 ttggattcgt catcggtaaa atgaatataa acatttatta gtgcaaataa acaatcaaaa 18780 tttaatatta aacaagatga aaaatatgac ctgatttttt gaaattattc tggttgtgaa 18840 aaaatatttg tatgattata caaatcgaaa tagttcaaac tctcaaaatg atgtctctcc 18900 ggaatctcgt gtattttcac gagtttcagt tctttcaaaa aacgtgccaa atattttctt 18960 ataaaacaaa tagtctttga ctaaatcaaa gattaccgtg atatgagatc ttaaaagtag 19020 cattggttat aagctattaa tatgattaat acgagatact gtaattgtag atttagttta 19080 gcttcatata tctctaattt aactttttaa gcctcgagtt aagtatttta catttgaaca 19140 attgtgtaat caaaacgcaa tcctgtacat aattattttc agcgctgtat tttctctcat 19200 caatcaaaaa atttaatttt taaaaataat ttgatttacc gagcatctga acagaagcaa 19260 ggacacgtga gtttgctgat tttgctgata agaaatcaat tatttaggtg cattggtgat 19320 cttcattctt tttctaaact tatcagaaaa aatatattct ctatttttaa catttattgt 19380 gttctacatg ttctacatgg ttttgtatat tcgtaacaat tttttaagta gaaaaaaata 19440 tatactgata atcagcaaaa actagttttt gttcacattt tgatatcatc acttttttat 19500 tatattcaac tagagtttaa aatattaatt ttattgattc ttatcgatat ttttgactat 19560 tgattcccgt gttgatcgct ttgtgataat aaaatttttg gaacaaatta gccaatcgtg 19620 cattttttgt catcaattca atattatctg acgattcctg ttcctgttag ttgcaaaatc 19680 atgaacaagt atcacttttc ctatatttta tttcatattt ttcccgtcat gaaacgttat 19740 gttttgcctc atataaatac aaaaatgaac aaaaaagtgg tgttcgactt gaaaacaaga 19800 tttttaggac agaaggtcgg atgggaaaag gttttcgttc gacggacatc acacaaaaaa 19860 gtatcacacc gcacctcatt ctatttactt tgttgataga atggaaaaac attcgactga 19920 aaatgaatac agagtaagtt tatttttcca aaaatgtttg aaataatgat tcaattttta 19980 ggtgtataag gaacgatggt ttattctttt ggcgactact gcattgattt gctcaaatat 20040 tatggtgagt aatggaatat tggtattttc atatttagat tggcgtgaat tttgctaaga 20100 agtccgatgt ttttccaaaa ttcaaataca ttacaaagta gtgccaaaat taaacatttt 20160 ttagattttt tgttttagct gaaaagtttg acgaggtgtt cataaattta aagagttttt 20220 gaaaacaaac ctttaattat gatgttcctg catttcttac aatttttgag gtaatttaat 20280 agaagacgag cctgccacaa aacggtttta ccagattttt caaactttaa caattattta 20340 ctggatttaa aataaaacat attaatgttt tttctgcagc aatgggtgag tttctcggct 20400 caaatcgacc aaacaaatat gtttttctgt ggcccaaatg aatataagaa ttgttcagca 20460 gccttcctat ctaatcaaat ctatcaggtt agatttttca attttgatcg gtataattta 20520 ttatattatt tttagatagt tgcagtaatt gtgagcatta taggaatgta ttttgcaaca 20580 gtttttggaa cacttccaac tgtatgtttc ttcttctaat ttacagtttt ctaatttaca 20640 cgtcttctag ctccgtctct cagcagtttt caatattgtt ggtgcagcaa tccgactcat 20700 tgcgtcactt ccaagccttc aaaacttttt ctggagacag tttttaatga ttattggaac 20760 tagcattgcc gcggctgctc aaatgtattt cgtcgtcttc tcgaaaattg cggaaagttg 20820 gttttatcca agacatcgag cttctgcaaa tgttgcatgt tcaaatagtc ttgagttagg 20880 agttgtactt ggaactgttt taccatcaat tattgtacca gcttctttta caaaagacat 20940 tgtcagttcc tggacatttt ttcttttggt tagttatgtc tctgtcatga ttaaacaact 21000 atattacaat ttcagaattc aataatagca gttgtatgta taattccatt atttttatta 21060 tttgttctat gccgtcgatc ggttccaaaa acgccaccat cagcctcatc gcaacatgag 21120 tcaagtggtc ctgtgacatc tggtattttt aaatgtttaa agtaagcccg tacttagctg 21180 tttaatttta attcttctga tagttctcag ggatcgtcag tttctcattc aaatattcgt 21240 ttattcaatt aattttgcaa ttgcaaatgg cctcatttat acttctaatg ccatcaacta 21300 tagaggttat aatttgaaag ggtacgtcta gtaaggtttt ctgctaggta caagaaatcc 21360 tactctgtca agtaggcagg catttttaga cctgcctagg aggtttaaac tcaagacagc 21420 cctttgcgta taattatttt gttcaggtat ccaatagcaa tcgccacgat ggtctgcatg 21480 ttttcagcct atttcgtagg agtaattgca gatagaacaa gaaagttcaa agttagtttc 21540 aaaaaatcta atcttatctg atatccattt ttctagttga tcgcaataat aaacgcactt 21600 gttgtagccg tttgtgtact ggtacttcgt ctggtaaggc tttttcaaaa taacattaaa 21660 tttattcatt aatgctttta gtatttaata aaaacttata cgggatggta tgattcagta 21720 attgtttgta cacttttaag cattatcagt aagttatttt aattttgctt atttagaata 21780 tattttcaaa aattcagtgt cctgttgtgc tatacataca ccgattggaa atgagatggg 21840 agttgagaca acttacccag ttcaagaatc aatttctaca ggagttttga atactttcgg 21900 gtgagccttt ggttcttttt acggcgaaaa aaagtgtgat atacccgctt ttttgggtct 21960 cgcagcgaat ttgtatttcg gtttgtgctt ttctgatatt aattttatac gagttttatt 22020 caaaacgaaa cgttaaaaag tttttcagtc aagcttggtt attctgctta tattttatta 22080 tgtattcttt acaagaatca aattgggttt acaagaacaa ccgtaaagga ggaagctggg 22140 aatgtaagtt tctttttaaa ttttaaaaca atgtttcaac taacgcggtc acttacaagc 22200 ctgtgtagct ttagtttcta actaattttc aaataattaa aagttttttt tctaatagta 22260 aataaaaata taaatattac gggaacacta aatactgaaa gtgcgtattg cacaacatat 22320 ttgacgcgaa aaatgatttg tagcgtagcg aaaactacag caacttttta gatgactacc 22380 gtagaactgg tttacggaac tcgtgtttca atcgataaaa tattaaaaga aaacacaaaa 22440 atgacaaaac aataaaaaaa aaactttaaa aaaaattgaa tattgttgtc acaattcgca 22500 caaatacttg tttcgtaact agagccccac ggcccgagaa gtggtacctg tacgcaattt 22560 gtctaccgta cacctggacg tttgggcgcg tttttctcaa aaacggctgg tccagttttt 22620 ttgtgatgca tataaaaaat gttcgaaatt aaattcaaaa ttttttggac caaagctttt 22680 tccttaaaac gagcccaaac ctggctaaac tgcaattatc aatagagcgc gtttacactg 22740 atgtaccctt tgccgggctg tgagcccgta aaccgacacc agcactaagt acagaagtca 22800 ttaaaataat tgttttaatg ttcgctacga tatatttccg ggtcaaatat gttgcgcaat 22860 acgcattttc aaaacgtagt gttcctgtta attatgtttt catttctgct tcaaaaacta 22920 aatattttat attacagtag cccttgactt ctgggcagga atgtctattc taaactttat 22980 tgtggctgta atattcttga gaccccgata taaccgttta caaatggaag aagaagctca 23040 aaatacacgg gaagcaattc gagattcagt gtatacaatt tgtaagtaat gaactgcttt 23100 tatttatcaa tgatgtaaat aataaaaaaa tgaatttgct gaaaaaaata aagtcatgag 23160 aaacaggaaa tgcgatatga gacaatggtg aaaaaagatt gggactagtt gaaactgggt 23220 gcaaatgaac tggtgaagtc tagaaacata atataaacat gtttgttggg caaaataatt 23280 tcaaattgag actatggtac atatgatttt ttaagtgaga aaatacaatt cctctaactt 23340 cttaagtaca aaatgctata aaatgcaaag taaatgcttg ctactatcgc atttcgatat 23400 ccgacgcagc cgttcgagct gtaacaggtt cctcattttc taatgccaat ttggcatttt 23460 ccagttctag acgacgatat ctgtaattga taaaattatt tattgagttt tgataaacgt 23520 ttataccgtg gtctcaaaaa gaacagtgat aagatgacag atacaattga gagcccacat 23580 gttacatcga gagcaactga aaaatattca tttacttcta ttttgaagat gataaaactt 23640 acatttccaa gattgtgcat agaacaagtg caacttttct gtgtaatttt gtgcaaatgg 23700 aataatgaac atgaaaagcg atccgaatat aacaagaaca cctgatgacg ttgcttccat 23760 tactgggaat gtcgtctcaa caccaagttc cactccaatc gggaattgag gtattgaaaa 23820 ggcacctgaa gaaatatagg aattttgtta tacaattaaa tttaaaaaat ccttaccgag 23880 acatccacaa agagtgtaaa cgattatgct atcaaagagc ccagtccgtg gttgatttag 23940 gaactgcaag tgtagccttt ttagattaaa aaaatccata gaggaaattt agacatattg 24000 acacaatttt tttcgaagac cctggtagaa gaattttaac tcaccattct caatgtaatg 24060 actgaacatg aaaatccaac agtacaaact ctgattattt cctaaatttt aaaattatat 24120 tttctttttc tgattcatac cgaccactca ccttgaactt gcgtgttttg tcggcaatat 24180 gaccagcgag cagtgatgtt aacgtgccaa cgattgcaca cacggcagtt ggatatctga 24240 aaaataaatg aattactcat atgcttctag aactctgcaa agttgttacc cagccatctc 24300 ataaccttga tctttgagtg gaccatcgag gaaaatcatt agactccaca gaagcgaaaa 24360 cgcaaatgca aagagagtca tttggatgaa aaattgagca ttactgaaat taaagtattt 24420 aaagtttttg gcgtgatact aaaaacctac aaaatacatt gaagaataga tttaaagaaa 24480 ccaatgttgt tctgatgagc agcagaagaa gctgatggtg gagtgggtgg cagtttagtt 24540 cgaacgaata gtgctagaac aaatgggaac aaggctagac attccattcc aagagtctga 24600 aaatatgaat tgtcaatgat aattaaattg agtactaaca aatgtgaaga acatccaact 24660 attcgaatca atagtcttat tgtgaccaaa aagaatggat ggcacaattg ttccgagggc 24720 aacaccggca ggatttgctg aaattgatag gaattactta cgaacattaa aattccacta 24780 accaacaaaa gaaagtacat ttgcaattgc tctctgatca ccagggaacc agcattcagc 24840 aatttttgat ggaagaacta aaaagaatgc ttgtgctgaa gcagcgataa acgatcctgc 24900 atgaagaaga cattcacgaa caaaatgtga ttttatgaaa ggaatcgagg caatcatccg 24960 aatcgatgct ccaattacat ttaaagttgt accaagaaga cc 25002 <210> SEQ ID NO 32 <211> LENGTH: 1237 <212> TYPE: PRT <213> ORGANISM: Rattus norvegicus <400> SEQUENCE: 32 Met Ala Arg Ala Lys Leu Pro Arg Ser Pro Ser Glu Gly Lys Ala Gly 1 5 10 15 Pro Gly Asp Thr Pro Ala Gly Ser Ala Ala Pro Glu Glu Pro His Gly 20 25 30 Leu Ser Pro Leu Leu Pro Thr Arg Gly Gly Gly Ser Val Gly Ser Asp 35 40 45 Val Gly Gln Arg Leu His Val Glu Asp Phe Ser Leu Asp Ser Ser Leu 50 55 60 Ser Gln Val Gln Val Glu Phe Tyr Val Asn Glu Asn Thr Phe Lys Glu 65 70 75 80 Arg Leu Lys Leu Phe Phe Ile Lys Asn Gln Arg Ser Ser Leu Arg Ile 85 90 95 Arg Leu Phe Asn Phe Ser Leu Lys Leu Leu Thr Cys Leu Leu Tyr Ile 100 105 110 Val Arg Val Leu Leu Asp Asn Pro Asp Gln Gly Ile Gly Cys Trp Gly 115 120 125 Cys Thr Lys Tyr Asn Tyr Thr Phe Asn Gly Ser Ser Ser Glu Phe His 130 135 140 Trp Ala Pro Ile Leu Trp Val Glu Arg Lys Met Ala Leu Trp Val Ile 145 150 155 160 Gln Val Ile Val Ala Thr Ile Ser Phe Leu Glu Thr Met Leu Leu Ile 165 170 175 Tyr Leu Ser Tyr Lys Gly Asn Ile Trp Glu Gln Ile Phe His Val Ser 180 185 190 Phe Val Leu Glu Met Ile Asn Thr Leu Pro Phe Ile Ile Thr Val Phe 195 200 205 Trp Pro Pro Leu Arg Asn Leu Phe Ile Pro Val Phe Leu Asn Cys Trp 210 215 220 Leu Ala Lys His Ala Leu Glu Asn Met Ile Asn Asp Phe His Arg Ala 225 230 235 240 Ile Leu Arg Thr Gln Ser Ala Met Phe Asn Gln Val Leu Ile Leu Phe 245 250 255 Cys Thr Leu Leu Cys Leu Val Phe Thr Gly Thr Cys Gly Ile Gln His 260 265 270 Leu Glu Arg Ala Gly Gly Asn Leu Asn Leu Leu Thr Ser Phe Tyr Phe 275 280 285 Cys Ile Val Thr Phe Ser Thr Val Gly Phe Gly Asp Val Thr Pro Lys 290 295 300 Ile Trp Pro Ser Gln Leu Leu Val Val Ile Leu Ile Cys Val Thr Leu 305 310 315 320 Val Val Leu Pro Leu Gln Phe Glu Glu Leu Val Tyr Leu Trp Met Glu 325 330 335 Arg Gln Lys Ser Gly Gly Asn Tyr Ser Arg His Arg Ala Arg Thr Glu 340 345 350 Lys His Val Val Leu Cys Val Ser Ser Leu Lys Ile Asp Leu Leu Met 355 360 365 Asp Phe Leu Asn Glu Phe Tyr Ala His Pro Arg Leu Gln Asp Tyr Tyr 370 375 380 Val Val Ile Leu Cys Pro Ser Glu Met Asp Val Gln Val Arg Arg Val 385 390 395 400 Leu Gln Ile Pro Leu Trp Ser Gln Arg Val Ile Tyr Leu Gln Gly Ser 405 410 415 Ala Leu Lys Asp Gln Asp Leu Met Arg Ala Lys Met Asp Asn Gly Glu 420 425 430 Ala Cys Phe Ile Leu Ser Ser Arg Asn Glu Val Asp Arg Thr Ala Ala 435 440 445 Asp His Gln Thr Ile Leu Arg Ala Trp Ala Val Lys Asp Phe Ala Pro 450 455 460 Asn Cys Pro Leu Tyr Val Gln Ile Leu Lys Pro Glu Asn Lys Phe His 465 470 475 480 Val Lys Phe Ala Asp His Val Val Cys Glu Glu Glu Cys Lys Tyr Ala 485 490 495 Met Leu Ala Leu Asn Cys Ile Cys Pro Ala Thr Ser Thr Leu Ile Thr 500 505 510 Leu Leu Val His Thr Ser Arg Gly Gln Glu Gly Gln Glu Ser Pro Glu 515 520 525 Gln Trp Gln Arg Met Tyr Gly Arg Cys Ser Gly Asn Glu Val Tyr His 530 535 540 Ile Arg Met Gly Asp Ser Lys Phe Phe Arg Glu Tyr Glu Gly Lys Ser 545 550 555 560 Phe Thr Tyr Ala Ala Phe His Ala His Lys Lys Tyr Gly Val Cys Leu 565 570 575 Ile Gly Leu Lys Arg Glu Glu Asn Lys Ser Ile Leu Leu Asn Pro Gly 580 585 590 Pro Arg His Ile Leu Ala Ala Ser Asp Thr Cys Phe Tyr Ile Asn Ile 595 600 605 Thr Lys Glu Glu Asn Ser Ala Phe Ile Phe Lys Gln Glu Glu Lys Gln 610 615 620 Asn Arg Arg Gly Leu Ala Gly Gln Ala Leu Tyr Glu Gly Pro Ser Arg 625 630 635 640 Leu Pro Val His Ser Ile Ile Ala Ser Met Val Ala Met Asp Leu Gln 645 650 655 Asn Thr Asp Cys Arg Pro Ser Gln Gly Gly Ser Gly Gly Gly Gly Gly 660 665 670 Lys Leu Thr Leu Pro Thr Glu Asn Gly Ser Gly Ser Arg Arg Pro Ser 675 680 685 Ile Ala Pro Val Leu Glu Leu Ala Asp Ser Ser Ala Leu Leu Pro Cys 690 695 700 Asp Leu Leu Ser Asp Gln Ser Glu Asp Glu Val Thr Pro Ser Asp Asp 705 710 715 720 Glu Gly Leu Ser Val Val Glu Tyr Val Lys Gly Tyr Pro Pro Asn Ser 725 730 735 Pro Tyr Ile Gly Ser Ser Pro Thr Leu Cys His Leu Leu Pro Val Lys 740 745 750 Ala Pro Phe Cys Cys Leu Arg Leu Asp Lys Gly Cys Lys His Asn Ser 755 760 765 Tyr Glu Asp Ala Lys Ala Tyr Gly Phe Lys Asn Lys Leu Ile Ile Val 770 775 780 Ser Ala Glu Thr Ala Gly Asn Gly Leu Tyr Asn Phe Ile Val Pro Leu 785 790 795 800 Arg Ala Tyr Tyr Arg Ser Arg Arg Glu Leu Asn Pro Ile Val Leu Leu 805 810 815 Leu Asp Asn Lys Pro Asp His His Phe Leu Glu Ala Ile Cys Cys Phe 820 825 830 Pro Met Val Tyr Tyr Met Glu Gly Ser Val Asp Asn Leu Asp Ser Leu 835 840 845 Leu Gln Cys Gly Ile Ile Tyr Ala Asp Asn Leu Val Val Val Asp Lys 850 855 860 Glu Ser Thr Met Ser Ala Glu Glu Asp Tyr Met Ala Asp Ala Lys Thr 865 870 875 880 Ile Val Asn Val Gln Thr Met Phe Arg Leu Phe Pro Ser Leu Ser Ile 885 890 895 Thr Thr Glu Leu Thr His Pro Ser Asn Met Arg Phe Met Gln Phe Arg 900 905 910 Ala Lys Asp Ser Tyr Ser Leu Ala Leu Ser Lys Leu Glu Lys Gln Glu 915 920 925 Arg Glu Asn Gly Ser Asn Leu Ala Phe Met Phe Arg Leu Pro Phe Ala 930 935 940 Ala Gly Arg Val Phe Ser Ile Ser Met Leu Asp Thr Leu Leu Tyr Gln 945 950 955 960 Ser Phe Val Lys Asp Tyr Met Ile Thr Ile Thr Arg Leu Leu Leu Gly 965 970 975 Leu Asp Thr Thr Pro Gly Ser Gly Tyr Leu Cys Ala Met Lys Val Thr 980 985 990 Glu Asp Asp Leu Trp Ile Arg Thr Tyr Gly Arg Leu Phe Gln Lys Leu 995 1000 1005 Cys Ser Ser Ser Ala Glu Ile Pro Ile Gly Ile Tyr Arg Thr Glu Cys 1010 1015 1020 His Val Phe Ser Ser Glu Pro His Asp Leu Arg Ala Gln Ser Gln Ile 1025 1030 1035 1040 Ser Val Asn Met Glu Asp Cys Glu Asp Thr Arg Glu Ala Lys Gly Pro 1045 1050 1055 Trp Gly Thr Arg Ala Ala Ser Gly Gly Gly Ser Thr His Gly Arg His 1060 1065 1070 Gly Gly Ser Ala Asp Pro Val Glu His Pro Leu Leu Arg Arg Lys Ser 1075 1080 1085 Leu Gln Trp Ala Arg Lys Leu Ser Arg Lys Ser Ser Lys Gln Ala Gly 1090 1095 1100 Lys Ala Pro Met Thr Thr Asp Trp Ile Thr Gln Gln Arg Leu Ser Leu 1105 1110 1115 1120 Tyr Arg Arg Ser Glu Arg Gln Glu Leu Ser Glu Leu Val Lys Asn Arg 1125 1130 1135 Met Lys His Leu Gly Leu Pro Thr Thr Gly Tyr Glu Asp Val Ala Asn 1140 1145 1150 Leu Thr Ala Ser Asp Val Met Asn Arg Val Asn Leu Gly Tyr Leu Gln 1155 1160 1165 Asp Glu Met Asn Asp His His Gln Asn Thr Leu Ser Tyr Val Leu Ile 1170 1175 1180 Asn Pro Pro Pro Asp Thr Arg Leu Glu Pro Asn Asp Ile Val Tyr Leu 1185 1190 1195 1200 Ile Arg Ser Asp Pro Leu Ala His Val Thr Ser Ser Ser Gln Ser Arg 1205 1210 1215 Lys Ser Ser Cys Ser Asn Lys Leu Ser Ser Cys Asn Pro Glu Thr Arg 1220 1225 1230 Asp Glu Thr Gln Leu 1235 <210> SEQ ID NO 33 <211> LENGTH: 638 <212> TYPE: PRT <213> ORGANISM: Rattus norvegicus <400> SEQUENCE: 33 Met Gly Lys Ile Glu Asn Asn Glu Arg Val Ile Leu Asn Val Gly Gly 1 5 10 15 Thr Arg His Glu Thr Tyr Arg Ser Thr Leu Lys Thr Leu Pro Gly Thr 20 25 30 Arg Leu Ala Leu Leu Ala Ser Ser Glu Pro Gln Gly Asp Cys Leu Thr 35 40 45 Ala Ala Gly Asp Lys Leu Gln Pro Leu Pro Pro Pro Leu Ser Pro Pro 50 55 60 Pro Arg Pro Pro Pro Leu Ser Pro Val Pro Ser Gly Cys Phe Glu Gly 65 70 75 80 Gly Ala Gly Asn Cys Ser Ser His Gly Gly Asn Gly Ser Asp His Pro 85 90 95 Gly Gly Gly Arg Glu Phe Phe Phe Asp Arg His Pro Gly Val Phe Ala 100 105 110 Tyr Val Leu Asn Tyr Tyr Arg Thr Gly Lys Leu His Cys Pro Ala Asp 115 120 125 Val Cys Gly Pro Leu Phe Glu Glu Glu Leu Ala Phe Trp Gly Ile Asp 130 135 140 Glu Thr Asp Val Glu Pro Cys Cys Trp Met Thr Tyr Arg Gln His Arg 145 150 155 160 Asp Ala Glu Glu Ala Leu Asp Ile Phe Glu Thr Pro Asp Leu Ile Gly 165 170 175 Gly Asp Pro Gly Asp Asp Glu Asp Leu Gly Gly Lys Arg Leu Gly Ile 180 185 190 Glu Asp Ala Ala Gly Leu Gly Gly Pro Asp Gly Lys Ser Gly Arg Trp 195 200 205 Arg Lys Leu Gln Pro Arg Met Trp Ala Leu Phe Glu Asp Pro Tyr Ser 210 215 220 Ser Arg Ala Ala Arg Phe Ile Ala Phe Ala Ser Leu Phe Phe Ile Leu 225 230 235 240 Val Ser Ile Thr Thr Phe Cys Leu Glu Thr His Glu Ala Phe Asn Ile 245 250 255 Val Lys Asn Lys Thr Glu Pro Val Ile Asn Gly Thr Ser Ala Val Leu 260 265 270 Gln Tyr Glu Ile Glu Thr Asp Pro Ala Leu Thr Tyr Val Glu Gly Val 275 280 285 Cys Val Val Trp Phe Thr Phe Glu Phe Leu Val Arg Ile Val Phe Ser 290 295 300 Pro Asn Lys Leu Glu Phe Ile Lys Asn Leu Leu Asn Ile Ile Asp Phe 305 310 315 320 Val Ala Ile Leu Pro Phe Tyr Leu Glu Val Gly Leu Ser Gly Leu Ser 325 330 335 Ser Lys Ala Ala Lys Asp Val Leu Gly Phe Leu Arg Val Val Arg Phe 340 345 350 Val Arg Ile Leu Arg Ile Phe Lys Leu Thr Arg His Phe Val Gly Leu 355 360 365 Arg Val Leu Gly His Thr Leu Arg Ala Ser Thr Asn Glu Phe Leu Leu 370 375 380 Leu Ile Ile Phe Leu Ala Leu Gly Val Leu Ile Phe Ala Thr Met Ile 385 390 395 400 Tyr Tyr Ala Glu Arg Val Gly Ala Gln Pro Asn Asp Pro Ser Ala Ser 405 410 415 Glu His Thr Gln Phe Lys Asn Ile Pro Ile Gly Phe Trp Trp Ala Val 420 425 430 Val Thr Met Thr Thr Leu Gly Tyr Gly Asp Met Tyr Pro Gln Thr Trp 435 440 445 Ser Gly Met Leu Val Gly Ala Leu Cys Ala Leu Ala Gly Val Leu Thr 450 455 460 Ile Ala Met Pro Val Pro Val Ile Val Asn Asn Phe Gly Met Tyr Tyr 465 470 475 480 Ser Leu Ala Met Ala Lys Gln Lys Leu Pro Arg Lys Arg Lys Lys His 485 490 495 Ile Pro Pro Ala Pro Leu Ala Ser Ser Pro Thr Phe Cys Lys Thr Glu 500 505 510 Leu Asn Met Ala Cys Asn Ser Thr Gln Ser Asp Thr Cys Leu Gly Lys 515 520 525 Glu Asn Arg Leu Leu Glu His Asn Arg Ser Val Leu Ser Gly Asp Asp 530 535 540 Ser Thr Gly Ser Glu Pro Pro Leu Ser Pro Pro Glu Arg Leu Pro Ile 545 550 555 560 Arg Arg Ser Ser Thr Arg Asp Lys Asn Arg Arg Gly Glu Thr Cys Phe 565 570 575 Leu Leu Thr Thr Gly Asp Tyr Thr Cys Ala Ser Asp Gly Gly Ile Arg 580 585 590 Lys Gly Tyr Glu Lys Ser Arg Ser Leu Asn Asn Ile Ala Gly Leu Ala 595 600 605 Gly Asn Ala Leu Arg Leu Ser Pro Val Thr Ser Pro Tyr Asn Ser Pro 610 615 620 Cys Pro Leu Arg Arg Ser Arg Ser Pro Ile Pro Ser Ile Leu 625 630 635 <210> SEQ ID NO 34 <211> LENGTH: 1187 <212> TYPE: PRT <213> ORGANISM: Mus musculus <400> SEQUENCE: 34 Met Asp Cys Ser Leu Leu Arg Thr Leu Val Arg Arg Tyr Cys Ala Gly 1 5 10 15 Glu Glu Asn Trp Val Asp Ser Arg Thr Ile Tyr Val Gly His Lys Glu 20 25 30 Pro Pro Pro Gly Ala Glu Ala Tyr Ile Pro Gln Arg Tyr Pro Asp Asn 35 40 45 Arg Ile Val Ser Ser Lys Tyr Thr Phe Trp Asn Phe Ile Pro Lys Asn 50 55 60 Leu Phe Glu Gln Phe Arg Arg Ile Ala Asn Phe Tyr Phe Leu Ile Ile 65 70 75 80 Phe Leu Val Gln Leu Ile Ile Asp Thr Pro Thr Ser Pro Val Thr Ser 85 90 95 Gly Leu Pro Leu Phe Phe Val Ile Thr Val Thr Ala Ile Lys Gln Gly 100 105 110 Tyr Glu Asp Trp Leu Arg His Lys Ala Asp Asn Ala Met Asn Gln Cys 115 120 125 Pro Val His Phe Ile Gln His Gly Lys Leu Val Arg Lys Gln Ser Arg 130 135 140 Lys Leu Arg Val Gly Asp Ile Val Met Val Lys Glu Asp Glu Thr Phe 145 150 155 160 Pro Cys Asp Leu Ile Phe Leu Ser Ser Asn Arg Ala Asp Gly Thr Cys 165 170 175 His Val Thr Thr Ala Ser Leu Asp Gly Glu Ser Ser His Lys Thr His 180 185 190 Tyr Ala Val Gln Asp Thr Lys Gly Phe His Thr Glu Ala Asp Val Asp 195 200 205 Ser Leu His Ala Thr Ile Glu Cys Glu Gln Pro Gln Pro Asp Leu Tyr 210 215 220 Lys Phe Val Gly Arg Ile Asn Val Tyr Asn Asp Leu Asn Asp Pro Val 225 230 235 240 Val Arg Pro Leu Gly Ser Glu Asn Leu Leu Leu Arg Gly Ala Thr Leu 245 250 255 Lys Asn Thr Glu Lys Ile Phe Gly Val Ala Ile Tyr Thr Gly Met Glu 260 265 270 Thr Lys Met Ala Leu Asn Tyr Gln Ser Lys Ser Gln Lys Arg Ser Ala 275 280 285 Val Glu Lys Ser Met Asn Thr Phe Leu Ile Val Tyr Leu Cys Ile Leu 290 295 300 Val Ser Lys Ala Leu Ile Asn Thr Val Leu Lys Tyr Val Trp Gln Ser 305 310 315 320 Glu Pro Phe Arg Asp Glu Pro Trp Tyr Asn Glu Lys Thr Glu Ser Glu 325 330 335 Arg Gln Arg Asn Leu Phe Leu Arg Ala Phe Thr Asp Phe Leu Ala Phe 340 345 350 Met Val Leu Phe Asn Tyr Ile Ile Pro Val Ser Met Tyr Val Thr Val 355 360 365 Glu Met Gln Lys Phe Leu Gly Ser Tyr Phe Ile Thr Trp Asp Glu Asp 370 375 380 Met Phe Asp Glu Glu Met Gly Glu Gly Pro Leu Val Asn Thr Ser Asp 385 390 395 400 Leu Asn Glu Glu Leu Gly Gln Val Glu Tyr Ile Phe Thr Asp Lys Thr 405 410 415 Gly Thr Leu Thr Glu Asn Asn Met Ala Phe Lys Glu Cys Cys Ile Glu 420 425 430 Gly His Val Tyr Val Pro His Val Ile Cys Asn Gly Gln Val Leu Pro 435 440 445 Asp Ser Ser Gly Ile Asp Met Ile Asp Ser Ser Pro Gly Val Cys Gly 450 455 460 Arg Glu Arg Glu Glu Leu Phe Phe Arg Ala Ile Cys Leu Cys His Thr 465 470 475 480 Val Gln Val Lys Asp Asp His Cys Gly Asp Asp Val Asp Gly Pro Gln 485 490 495 Lys Ser Pro Asp Ala Lys Ser Cys Val Tyr Ile Ser Ser Ser Pro Asp 500 505 510 Glu Val Ala Leu Val Glu Gly Val Gln Arg Leu Gly Phe Thr Tyr Leu 515 520 525 Arg Leu Lys Asp Asn Tyr Met Glu Ile Leu Asn Arg Glu Asn Asp Ile 530 535 540 Glu Arg Phe Glu Leu Leu Glu Val Leu Thr Phe Asp Ser Val Arg Arg 545 550 555 560 Arg Met Ser Val Ile Val Lys Ser Thr Thr Gly Glu Ile Tyr Leu Phe 565 570 575 Cys Lys Gly Ala Asp Ser Ser Ile Phe Pro Arg Val Ile Glu Gly Lys 580 585 590 Val Asp Gln Val Arg Ser Arg Val Glu Arg Asn Ala Val Glu Gly Leu 595 600 605 Arg Thr Leu Cys Val Ala Tyr Lys Arg Leu Glu Pro Glu Gln Tyr Glu 610 615 620 Asp Ala Cys Arg Leu Leu Gln Ser Ala Lys Val Ala Leu Gln Asp Arg 625 630 635 640 Glu Lys Lys Leu Ala Glu Ala Tyr Glu Gln Ile Glu Lys Asp Leu Val 645 650 655 Leu Leu Gly Ala Thr Ala Val Glu Asp Arg Leu Gln Glu Lys Ala Ala 660 665 670 Asp Thr Ile Glu Ala Leu Gln Lys Ala Gly Ile Lys Val Trp Val Leu 675 680 685 Thr Gly Asp Lys Met Glu Thr Ala Ser Ala Thr Cys Tyr Ala Cys Lys 690 695 700 Leu Phe Arg Arg Ser Thr Gln Leu Leu Glu Leu Thr Thr Lys Lys Leu 705 710 715 720 Glu Glu Gln Ser Leu His Asp Val Leu Phe Asp Leu Ser Lys Thr Val 725 730 735 Leu Arg Cys Ser Gly Ser Met Thr Arg Asp Ser Phe Ser Gly Leu Ser 740 745 750 Thr Asp Met His Asp Tyr Gly Leu Ile Ile Asp Gly Ala Ala Leu Ser 755 760 765 Leu Ile Met Lys Pro Arg Glu Asp Gly Ser Ser Ser Gly Asn Tyr Arg 770 775 780 Glu Leu Phe Leu Glu Ile Cys Arg Asn Cys Ser Ala Val Leu Cys Cys 785 790 795 800 Arg Met Ala Pro Leu Gln Lys Ala Gln Ile Val Lys Leu Ile Lys Phe 805 810 815 Ser Lys Glu His Pro Ile Thr Leu Ala Ile Gly Asp Gly Ala Asn Asp 820 825 830 Val Ser Met Ile Leu Glu Ala His Val Gly Ile Gly Val Ile Gly Lys 835 840 845 Glu Gly Arg Gln Ala Ala Arg Asn Ser Asp Tyr Ala Ile Pro Lys Phe 850 855 860 Lys His Leu Lys Lys Met Leu Leu Val His Gly His Phe Tyr Tyr Ile 865 870 875 880 Arg Ile Ser Glu Leu Val Gln Tyr Phe Phe Tyr Lys Asn Val Cys Phe 885 890 895 Ile Phe Pro Gln Phe Leu Tyr Gln Phe Phe Cys Gly Phe Ser Gln Gln 900 905 910 Thr Leu Tyr Asp Thr Ala Tyr Leu Thr Leu Tyr Asn Ile Ser Phe Thr 915 920 925 Ser Leu Pro Ile Leu Leu Tyr Ser Leu Met Glu Gln His Val Gly Ile 930 935 940 Asp Val Leu Lys Arg Asp Pro Thr Leu Tyr Arg Asp Ile Ala Lys Asn 945 950 955 960 Ala Leu Leu Arg Trp Arg Val Phe Ile Tyr Trp Thr Phe Leu Gly Val 965 970 975 Phe Asp Ala Leu Val Phe Phe Phe Gly Ala Tyr Phe Ile Phe Glu Asn 980 985 990 Thr Thr Val Thr Ile Asn Gly Gln Met Phe Gly Asn Trp Thr Phe Gly 995 1000 1005 Thr Leu Val Phe Thr Val Met Val Leu Thr Val Thr Leu Lys Leu Ala 1010 1015 1020 Leu Asp Thr His Tyr Trp Thr Trp Ile Asn His Phe Val Ile Trp Gly 1025 1030 1035 1040 Ser Leu Leu Phe Tyr Ile Ala Phe Ser Leu Leu Trp Gly Gly Val Ile 1045 1050 1055 Trp Pro Phe Leu Ser Tyr Gln Arg Met Tyr Tyr Val Phe Ile Ser Met 1060 1065 1070 Leu Ser Ser Gly Pro Ala Trp Leu Gly Ile Ile Leu Leu Val Thr Val 1075 1080 1085 Gly Leu Leu Pro Asp Val Leu Lys Lys Val Leu Cys Arg Gln Leu Trp 1090 1095 1100 Pro Thr Ala Thr Glu Arg Thr Gln Asn Ile Gln His Gln Asp Ser Ile 1105 1110 1115 1120 Ser Glu Phe Thr Pro Leu Ala Ser Leu Pro Ser Trp Gly Ala Gln Gly 1125 1130 1135 Ser Arg Leu Leu Ala Ala Gln Cys Ser Ser Pro Ser Gly Arg Val Val 1140 1145 1150 Cys Ser Arg Trp Glu Ser Glu Glu Cys Pro Val Leu Pro Leu His Pro 1155 1160 1165 Gly Leu Pro His Lys Ala Arg Tyr Gly Cys Cys Arg Ser Ser Leu Glu 1170 1175 1180 Met Pro Thr 1185 <210> SEQ ID NO 35 <211> LENGTH: 1508 <212> TYPE: PRT <213> ORGANISM: Mus musculus <400> SEQUENCE: 35 Met Glu Arg Glu Leu Pro Ala Ala Glu Glu Ser Ala Ser Ser Gly Trp 1 5 10 15 Arg Arg Pro Arg Arg Arg Arg Trp Glu Gly Arg Thr Arg Thr Val Arg 20 25 30 Ser Asn Leu Leu Pro Pro Leu Gly Thr Glu Asp Ser Thr Ile Gly Ala 35 40 45 Pro Lys Gly Glu Arg Leu Leu Met Arg Gly Cys Ile Gln His Leu Ala 50 55 60 Asp Asn Arg Leu Lys Thr Thr Lys Tyr Thr Leu Leu Ser Phe Leu Pro 65 70 75 80 Lys Asn Leu Phe Glu Gln Phe His Arg Leu Ala Asn Val Tyr Phe Val 85 90 95 Phe Ile Ala Leu Leu Asn Phe Val Pro Ala Val Asn Ala Phe Gln Pro 100 105 110 Gly Leu Ala Leu Ala Pro Val Leu Phe Ile Leu Ala Val Thr Ala Ile 115 120 125 Lys Asp Leu Trp Glu Asp Tyr Ser Arg His Arg Ser Asp His Glu Ile 130 135 140 Asn His Leu Gly Cys Leu Val Phe Ser Arg Glu Glu Lys Lys Tyr Val 145 150 155 160 Asn Arg Tyr Trp Lys Glu Ile Arg Val Gly Asp Phe Val Arg Leu Cys 165 170 175 Cys Asn Glu Ile Ile Pro Ala Asp Ile Leu Leu Leu Ser Ser Ser Asp 180 185 190 Pro Asp Gly Leu Cys His Ile Glu Thr Ala Asn Leu Asp Gly Glu Thr 195 200 205 Asn Leu Lys Arg Arg Gln Val Val Arg Gly Phe Ser Glu Leu Val Ser 210 215 220 Glu Phe Asn Pro Leu Thr Phe Thr Ser Val Ile Glu Cys Glu Lys Pro 225 230 235 240 Asn Asn Asp Leu Ser Arg Phe Arg Gly Tyr Ile Met His Ser Asn Gly 245 250 255 Glu Lys Ala Gly Leu His Lys Glu Asn Leu Leu Leu Arg Gly Cys Thr 260 265 270 Ile Arg Asn Thr Glu Ala Val Ala Gly Ile Val Ile Tyr Ala Gly His 275 280 285 Glu Thr Lys Ala Leu Leu Asn Asn Ser Gly Pro Arg Tyr Lys Arg Ser 290 295 300 Gln Leu Glu Arg Gln Met Asn Cys Asp Val Leu Trp Cys Val Leu Leu 305 310 315 320 Leu Val Cys Ile Ser Leu Phe Ser Ala Val Gly His Gly Leu Trp Val 325 330 335 Arg Arg Tyr Gln Glu Lys Lys Ala Leu Phe Asp Val Pro Glu Ser Asp 340 345 350 Gly Ser Ser Leu Ser Pro Ala Thr Ala Ala Val Tyr Ser Phe Phe Thr 355 360 365 Met Ile Ile Val Leu Gln Val Leu Ile Pro Ile Ser Leu Tyr Val Ser 370 375 380 Ile Glu Ile Val Lys Val Cys Gln Val Tyr Phe Ile Asn Gln Asp Ile 385 390 395 400 Glu Leu Tyr Asp Glu Glu Thr Asp Ser Gln Leu Gln Cys Arg Ala Leu 405 410 415 Asn Ile Thr Glu Asp Leu Gly Gln Ile Lys Tyr Ile Phe Ser Asp Lys 420 425 430 Thr Gly Thr Leu Thr Glu Asn Lys Met Val Phe Arg Arg Cys Thr Val 435 440 445 Ser Gly Ile Glu Tyr Ser His Asp Ala Asn Ala Gln Arg Leu Ala Arg 450 455 460 Tyr Gln Glu Ala Asp Ser Glu Glu Glu Glu Val Val Ser Lys Val Gly 465 470 475 480 Thr Ile Ser His Arg Gly Ser Thr Gly Ser His Gln Ser Ile Trp Met 485 490 495 Thr His Lys Thr Gln Ser Ile Lys Ser His Arg Arg Thr Gly Ser Arg 500 505 510 Ala Glu Ala Lys Arg Ala Ser Met Leu Ser Lys His Thr Ala Phe Ser 515 520 525 Ser Pro Met Glu Lys Asp Ile Thr Pro Asp Pro Lys Leu Leu Glu Lys 530 535 540 Val Ser Glu Cys Asp Arg Phe Leu Ala Ile Ala Arg His Gln Glu His 545 550 555 560 Pro Leu Ala His Leu Ser Pro Glu Leu Ser Asp Val Phe Asp Phe Phe 565 570 575 Ile Ala Leu Thr Ile Cys Asn Thr Val Val Val Thr Ser Pro Asp Gln 580 585 590 Pro Arg Gln Lys Val Arg Val Arg Phe Glu Leu Lys Ser Pro Val Lys 595 600 605 Thr Ile Glu Asp Phe Leu Arg Arg Phe Thr Pro Ser Arg Leu Ala Ser 610 615 620 Gly Cys Ser Ser Ile Gly Asn Leu Ser Thr Ser Lys Ser Ser His Lys 625 630 635 640 Ser Gly Ser Ala Phe Leu Pro Ser Leu Ser Gln Asp Ser Met Leu Leu 645 650 655 Gly Leu Glu Glu Lys Leu Gly Gln Thr Ala Pro Ser Ile Ala Ser Asn 660 665 670 Gly Tyr Ala Ser Gln Ala Gly Gln Glu Glu Ser Trp Ala Ser Asp Cys 675 680 685 Thr Thr Asp Gln Lys Cys Pro Gly Glu Gln Arg Glu Gln Gln Glu Gly 690 695 700 Glu Leu Arg Tyr Glu Ala Glu Ser Pro Asp Glu Ala Ala Leu Val Tyr 705 710 715 720 Ala Ala Arg Ala Tyr Asn Cys Ala Leu Val Asp Arg Leu His Asp Gln 725 730 735 Val Ser Val Glu Leu Pro His Leu Gly Arg Leu Thr Phe Glu Leu Leu 740 745 750 His Thr Leu Gly Phe Asp Ser Ile Arg Lys Arg Met Ser Val Val Ile 755 760 765 Arg His Pro Leu Thr Asp Glu Ile Asn Val Tyr Thr Lys Gly Ala Asp 770 775 780 Ser Val Val Met Asp Leu Leu Leu Pro Cys Ser Ser Asp Asp Ala Arg 785 790 795 800 Gly Arg His Gln Lys Lys Ile Arg Ser Lys Thr Gln Asn Tyr Leu Asn 805 810 815 Leu Tyr Ala Val Glu Gly Leu Arg Thr Leu Cys Ile Ala Lys Arg Val 820 825 830 Leu Ser Lys Glu Glu Tyr Ala Cys Trp Leu Gln Ser His Ile Glu Ala 835 840 845 Glu Ala Ser Val Glu Ser Arg Glu Glu Leu Leu Phe Gln Ser Ala Val 850 855 860 Arg Leu Glu Thr Asn Leu His Leu Leu Gly Ala Thr Gly Ile Glu Asp 865 870 875 880 Arg Leu Gln Glu Gly Val Pro Glu Thr Ile Ala Lys Leu Arg Gln Ala 885 890 895 Gly Leu Gln Ile Trp Val Leu Thr Gly Asp Lys Gln Glu Thr Ala Ile 900 905 910 Asn Ile Ala Tyr Ala Cys Lys Leu Leu Asp His Gly Glu Glu Val Ile 915 920 925 Thr Leu Asn Ala Asp Ser Gln Glu Ala Cys Ala Ala Leu Leu Asp Gln 930 935 940 Cys Leu Ser Tyr Val Gln Ser Arg Asn Pro Arg Ser Thr Leu Gln Asn 945 950 955 960 Ser Glu Ser Asn Leu Ser Val Gly Phe Ser Phe Asn Pro Val Ser Thr 965 970 975 Ser Thr Asp Ala Ser Pro Ser Pro Ser Leu Val Ile Asp Gly Arg Ser 980 985 990 Leu Ala Tyr Ala Leu Glu Lys Ser Leu Glu Asp Lys Phe Leu Phe Leu 995 1000 1005 Ala Lys Gln Cys Arg Ser Val Leu Cys Cys Arg Ser Thr Pro Leu Gln 1010 1015 1020 Lys Ser Met Val Val Lys Leu Val Arg Ser Lys Leu Lys Ala Met Thr 1025 1030 1035 1040 Leu Ala Ile Gly Asp Gly Ala Asn Asp Val Ser Met Ile Gln Val Ala 1045 1050 1055 Asp Val Gly Val Gly Ile Ser Gly Gln Glu Gly Met Gln Ala Val Met 1060 1065 1070 Ala Ser Asp Phe Ala Val Pro Arg Phe Arg Tyr Leu Glu Arg Leu Leu 1075 1080 1085 Ile Val His Gly His Trp Cys Tyr Ser Arg Leu Ala Asn Met Val Leu 1090 1095 1100 Tyr Phe Phe Tyr Lys Asn Thr Met Ser Val Gly Leu Leu Phe Trp Phe 1105 1110 1115 1120 Gln Phe Tyr Cys Gly Phe Ser Ala Ser Ala Met Ile Asp Gln Trp Tyr 1125 1130 1135 Leu Ile Phe Phe Asn Leu Leu Phe Ser Ser Leu Pro Gln Leu Val Thr 1140 1145 1150 Gly Val Leu Asp Lys Asp Val Pro Ala Asp Met Leu Leu Arg Glu Pro 1155 1160 1165 Gln Leu Tyr Lys Ser Gly Gln Asn Met Glu Glu Tyr Arg Pro Arg Ala 1170 1175 1180 Phe Trp Leu Asn Met Val Asp Ala Ala Phe Gln Ser Leu Val Cys Phe 1185 1190 1195 1200 Phe Ile Pro Tyr Leu Ala Tyr Tyr Asp Ser Asp Val Asp Val Phe Thr 1205 1210 1215 Trp Gly Thr Pro Val Thr Ala Ile Ala Leu Phe Thr Phe Leu Leu His 1220 1225 1230 Leu Gly Ile Glu Thr Lys Thr Trp Thr Trp Leu Asn Trp Leu Ala Cys 1235 1240 1245 Gly Phe Ser Thr Phe Leu Phe Phe Ser Val Ala Leu Ile Tyr Asn Thr 1250 1255 1260 Ser Cys Ala Thr Cys Tyr Pro Pro Ser Asn Pro Tyr Trp Thr Met Gln 1265 1270 1275 1280 Thr Leu Leu Gly Asp Pro Leu Phe Tyr Leu Thr Cys Leu Ile Ala Pro 1285 1290 1295 Ile Ala Ala Leu Leu Pro Arg Leu Phe Phe Lys Ala Leu Gln Gly Ser 1300 1305 1310 Leu Phe Pro Thr Gln Leu Gln Leu Gly Arg Gln Leu Ala Lys Lys Pro 1315 1320 1325 Leu Asn Lys Phe Ser Asp Pro Lys Glu Thr Phe Ala Gln Gly Gln Pro 1330 1335 1340 Pro Gly His Ser Glu Thr Glu Leu Ser Glu Arg Lys Thr Met Gly Pro 1345 1350 1355 1360 Phe Glu Thr Leu Pro Arg Asp Cys Ala Ser Gln Ala Ser Gln Phe Thr 1365 1370 1375 Gln Gln Leu Thr Cys Ser Pro Glu Ala Ser Gly Glu Pro Ser Ala Val 1380 1385 1390 Asp Thr Asn Met Pro Leu Arg Glu Asn Thr Leu Leu Glu Gly Leu Gly 1395 1400 1405 Ser Gln Ala Ser Gly Ser Ser Met Pro Arg Gly Ala Ile Ser Glu Val 1410 1415 1420 Cys Pro Gly Asp Ser Lys Arg Gln Ser Ser Ser Ala Ser Gln Thr Ala 1425 1430 1435 1440 Arg Leu Ser Ser Leu Phe His Leu Pro Ser Phe Gly Ser Leu Asn Trp 1445 1450 1455 Ile Ser Ser Leu Ser Leu Ala Ser Gly Leu Gly Ser Val Leu Gln Leu 1460 1465 1470 Ser Gly Ser Ser Leu Gln Met Asp Lys Gln Asp Gly Glu Phe Leu Ser 1475 1480 1485 Asn Pro Pro Gln Pro Glu Gln Asp Leu His Ser Phe Gln Gly Gln Val 1490 1495 1500 Thr Gly Tyr Leu 1505 <210> SEQ ID NO 36 <211> LENGTH: 1095 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <221> NAME/KEY: VARIANT <222> LOCATION: 801, 1005 <223> OTHER INFORMATION: Xaa = any amino acid <400> SEQUENCE: 36 Met Pro Leu Met Met Ser Glu Glu Gly Phe Glu Asn Asp Glu Ser Asp 1 5 10 15 Tyr His Thr Leu Pro Arg Ala Arg Ile Thr Arg Arg Lys Arg Gly Leu 20 25 30 Glu Trp Phe Val Cys Gly Gly Trp Lys Phe Leu Cys Thr Ser Cys Cys 35 40 45 Asp Trp Leu Ile Asn Val Cys Gln Arg Lys Lys Glu Leu Lys Ala Arg 50 55 60 Thr Val Trp Leu Gly Cys Pro Glu Lys Cys Glu Glu Lys His Pro Arg 65 70 75 80 Asn Ser Ile Lys Asn Gln Lys Tyr Asn Val Phe Thr Phe Ile Pro Gly 85 90 95 Val Leu Tyr Glu Gln Phe Lys Phe Phe Leu Asn Leu Tyr Phe Leu Val 100 105 110 Val Ser Cys Ser Gln Phe Val Pro Ala Leu Lys Ile Gly Tyr Leu Tyr 115 120 125 Thr Tyr Trp Ala Pro Leu Gly Phe Val Leu Ala Val Thr Ile Ala Arg 130 135 140 Glu Ala Ile Asp Glu Phe Arg Arg Phe Gln Arg Asp Lys Glu Met Asn 145 150 155 160 Ser Gln Leu Tyr Ser Lys Leu Thr Val Arg Gly Lys Val Gln Val Lys 165 170 175 Ser Ser Asp Ile Gln Val Gly Asp Leu Ile Ile Val Glu Lys Asn Gln 180 185 190 Arg Ile Pro Ser Asp Met Val Phe Leu Arg Thr Ser Glu Lys Ala Gly 195 200 205 Ser Cys Phe Ile Arg Thr Asp Gln Leu Asp Gly Glu Thr Asp Trp Lys 210 215 220 Leu Lys Val Ala Val Ser Cys Thr Gln Arg Leu Pro Ala Leu Gly Asp 225 230 235 240 Leu Phe Ser Ile Ser Ala Tyr Val Tyr Ala Gln Lys Pro Gln Leu Asp 245 250 255 Ile His Ser Phe Glu Gly Thr Phe Thr Arg Glu Asp Ser Asp Pro Pro 260 265 270 Ile His Glu Ser Leu Ser Ile Glu Asn Thr Leu Trp Ala Ser Thr Ile 275 280 285 Val Ala Ser Gly Thr Val Ile Gly Val Val Ile Tyr Thr Gly Lys Glu 290 295 300 Thr Arg Ser Val Met Asn Thr Ser Asn Pro Asn Asn Lys Val Gly Leu 305 310 315 320 Leu Asp Leu Glu Leu Asn Gln Leu Thr Lys Ala Leu Phe Leu Ala Leu 325 330 335 Val Val Leu Ser Val Val Met Val Thr Leu Gln Gly Phe Ala Gly Pro 340 345 350 Trp Tyr Arg Asn Leu Phe Arg Phe Leu Leu Leu Phe Ser Tyr Ile Ile 355 360 365 Pro Ile Ser Leu Arg Val Asn Leu Asp Met Gly Lys Ala Ala Tyr Gly 370 375 380 Trp Met Ile Met Lys Asp Glu Asn Ile Pro Gly Thr Val Val Arg Thr 385 390 395 400 Ser Thr Ile Pro Glu Glu Leu Gly Arg Leu Val Tyr Leu Leu Thr Asp 405 410 415 Lys Thr Gly Thr Leu Thr Gln Asn Glu Met Val Phe Lys Arg Leu His 420 425 430 Leu Gly Thr Val Ser Tyr Gly Thr Asp Thr Met Asp Glu Ile Gln Ser 435 440 445 His Val Leu Asn Ser Tyr Leu Gln Val His Ser Gln Pro Ser Gly His 450 455 460 Asn Pro Ser Ser Ala Pro Leu Arg Arg Ser Gln Ser Ser Thr Pro Lys 465 470 475 480 Val Lys Lys Ser Val Ser Ser Arg Ile His Glu Ala Val Lys Ala Ile 485 490 495 Ala Leu Cys His Asn Val Thr Pro Val Tyr Glu Ala Arg Ala Gly Ile 500 505 510 Thr Gly Glu Thr Glu Phe Ala Glu Ala Asp Gln Asp Phe Ser Asp Glu 515 520 525 Asn Arg Thr Tyr Gln Ala Ser Ser Pro Asp Glu Val Ala Leu Val Arg 530 535 540 Trp Thr Glu Ser Val Gly Leu Thr Leu Val Ser Arg Asp Leu Ala Ser 545 550 555 560 Met Gln Leu Lys Thr Pro Ser Gly Gln Val Leu Thr Tyr Cys Ile Leu 565 570 575 Gln Met Phe Pro Phe Thr Ser Glu Ser Lys Arg Met Gly Ile Ile Val 580 585 590 Arg Asp Glu Ser Thr Ala Glu Ile Thr Phe Tyr Met Lys Gly Ala Asp 595 600 605 Val Ala Met Ser Thr Ile Val Gln Tyr Asn Asp Trp Leu Glu Glu Glu 610 615 620 Cys Gly Asn Met Ala Arg Glu Gly Leu Arg Thr Leu Val Val Ala Lys 625 630 635 640 Arg Thr Leu Thr Glu Glu Gln Tyr Gln Asp Phe Glu Ser Arg Tyr Ser 645 650 655 Gln Ala Lys Leu Ser Ile His Asp Arg Ala Leu Lys Val Ala Ala Val 660 665 670 Val Glu Ser Leu Glu Arg Glu Met Glu Leu Leu Cys Leu Thr Gly Val 675 680 685 Glu Asp Gln Leu Gln Ala Asp Val Arg Pro Thr Leu Glu Met Leu Arg 690 695 700 Asn Ala Gly Ile Lys Ile Trp Met Leu Thr Gly Asp Lys Leu Glu Thr 705 710 715 720 Ala Thr Cys Ile Ala Lys Ser Ser His Leu Val Ser Arg Thr Gln Asp 725 730 735 Ile His Val Phe Arg Pro Val Thr Ser Arg Gly Glu Ala His Leu Glu 740 745 750 Leu Asn Ala Phe Arg Arg Lys His Asp Cys Ala Leu Val Ile Ser Gly 755 760 765 Asp Ser Leu Glu Val Cys Leu Arg Tyr Tyr Glu His Glu Leu Val Glu 770 775 780 Leu Ala Cys Gln Cys Pro Ala Val Val Cys Cys Arg Cys Ser Pro Thr 785 790 795 800 Xaa Lys Ala His Ile Val Thr Leu Leu Arg Gln His Thr Arg Lys Arg 805 810 815 Thr Cys Ala Ile Gly Asp Gly Gly Asn Asp Val Ser Met Ile Gln Ala 820 825 830 Ala Asp Cys Gly Ile Gly Ile Glu Gly Lys Glu Gly Lys Gln Ala Ser 835 840 845 Leu Ala Ala Asp Phe Ser Ile Thr Gln Phe Arg His Ile Gly Arg Leu 850 855 860 Leu Met Val His Gly Arg Asn Ser Tyr Lys Arg Ser Ala Ala Leu Gly 865 870 875 880 Gln Phe Val Met His Arg Gly Leu Ile Ile Ser Thr Met Gln Ala Val 885 890 895 Phe Ser Ser Val Phe Tyr Phe Ala Ser Val Pro Leu Tyr Gln Gly Phe 900 905 910 Leu Met Val Gly Tyr Ala Thr Ile Tyr Thr Met Phe Pro Val Phe Ser 915 920 925 Leu Val Leu Asp Gln Asp Val Lys Pro Glu Met Ala Ile Leu Tyr Pro 930 935 940 Glu Leu Tyr Lys Asp Leu Thr Lys Gly Arg Ser Leu Ser Phe Lys Thr 945 950 955 960 Phe Leu Ile Trp Val Leu Ile Ser Ile Tyr Gln Gly Gly Ile Leu Met 965 970 975 Tyr Gly Ala Leu Leu Leu Phe Glu Asp Glu Phe Val His Val Val Ala 980 985 990 Ile Ser Phe Thr Ala Leu Ile Leu Thr Glu Leu Leu Xaa Val Ala Leu 995 1000 1005 Thr Ile Arg Thr Trp His Trp Leu Met Val Val Ala Glu Phe Leu Ser 1010 1015 1020 Leu Gly Cys Tyr Val Ala Ser Leu Ala Phe Leu Asn Glu Tyr Phe Gly 1025 1030 1035 1040 Ile Gly Arg Val Ser Phe Gly Ala Phe Leu Asp Val Ala Phe Ile Thr 1045 1050 1055 Thr Val Thr Phe Leu Trp Lys Val Ser Ala Ile Thr Val Val Ser Cys 1060 1065 1070 Leu Pro Leu Tyr Val Leu Lys Tyr Leu Lys Arg Lys Leu Ser Pro Pro 1075 1080 1085 Ser Tyr Ser Lys Leu Ser Ser 1090 1095 <210> SEQ ID NO 37 <211> LENGTH: 9 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: domain <221> NAME/KEY: VARIANT <222> LOCATION: (1) <223> OTHER INFORMATION: Xaa = Asp, Asn, or Ser <221> NAME/KEY: VARIANT <222> LOCATION: (2) <223> OTHER INFORMATION: Xaa = Gln, Glu, Asn, or Arg <221> NAME/KEY: VARIANT <222> LOCATION: (3) <223> OTHER INFORMATION: Xaa = Ser or Ala <221> NAME/KEY: VARIANT <222> LOCATION: (4) <223> OTHER INFORMATION: Xaa = Leu, Ile, Val. Ser, Ala, or Asn <221> NAME/KEY: VARIANT <222> LOCATION: (5) <223> OTHER INFORMATION: Xaa = Leu, Ile, or Val <221> NAME/KEY: VARIANT <222> LOCATION: (6) <223> OTHER INFORMATION: Xaa = Thr, Ser, or Asn <221> NAME/KEY: VARIANT <222> LOCATION: (9) <223> OTHER INFORMATION: Xaa = Ser or Asn <400> SEQUENCE: 37 Xaa Xaa Xaa Xaa Xaa Xaa Gly Glu Xaa 1 5 <210> SEQ ID NO 38 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: domain <221> NAME/KEY: VARIANT <222> LOCATION: (1) <223> OTHER INFORMATION: Xaa = Leu, Ile, or Val <221> NAME/KEY: VARIANT <222> LOCATION: (2) <223> OTHER INFORMATION: Xaa = Cys, Ala, Met, or Leu <221> NAME/KEY: VARIANT <222> LOCATION: (3) <223> OTHER INFORMATION: Xaa = Ser, Thr, Phe, or Leu <221> NAME/KEY: VARIANT <222> LOCATION: (9) <223> OTHER INFORMATION: Xaa = Leu or Ile <400> SEQUENCE: 38 Xaa Xaa Xaa Asp Lys Thr Gly Thr Xaa Thr 1 5 10 <210> SEQ ID NO 39 <211> LENGTH: 11 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: domain <221> NAME/KEY: VARIANT <222> LOCATION: (1) <223> OTHER INFORMATION: Xaa = Thr, Ile, or Val <221> NAME/KEY: VARIANT <222> LOCATION: (5) <223> OTHER INFORMATION: Xaa = any amino acid <221> NAME/KEY: VARIANT <222> LOCATION: (8) <223> OTHER INFORMATION: Xaa = Ala, Ser, or Gly <221> NAME/KEY: VARIANT <222> LOCATION: (10) <223> OTHER INFORMATION: Xaa = Ala, Ser, or Val <400> SEQUENCE: 39 Xaa Gly Asp Gly Xaa Asn Asp Xaa Pro Xaa Leu 1 5 10 <210> SEQ ID NO 40 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: domain <221> NAME/KEY: VARIANT <222> LOCATION: (6) <223> OTHER INFORMATION: Xaa = Leu, Ile, Val, or Met <221> NAME/KEY: VARIANT <222> LOCATION: (7) <223> OTHER INFORMATION: Xaa = Thr or Ile <400> SEQUENCE: 40 Asp Lys Thr Gly Thr Xaa Xaa 1 5 

What is claimed:
 1. An isolated nucleic acid molecule selected from the group consisting of: (a) a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, or SEQ ID NO:13, SEQ ID NO:16, SEQ ID NO:19, SEQ ID NO:22, or SEQ ID NO:25; and (b) a nucleic acid molecule comprising the nucleotide sequence set forth in SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:9, SEQ ID NO:12, or SEQ ID NO:15, SEQ ID NO:18, SEQ ID NO:21, SEQ ID NO:24, or SEQ ID NO:27.
 2. An isolated nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID No:26.
 3. An isolated nucleic acid molecule comprising the nucleotide sequence contained in the plasmid deposited with ATCC® as Accession Number ______, ______, ______, ______, or ______.
 4. An isolated nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:l 1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26.
 5. An isolated nucleic acid molecule selected from the group consisting of: a) a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or a complement thereof; b) a nucleic acid molecule comprising a fragment of at least 30 nucleotides of a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, or a complement thereof; c) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence at least about 60% identical to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26; and d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, wherein the fragment comprises at least 10 contiguous amino acid residues of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26.
 6. An isolated nucleic acid molecule which hybridizes to a complement of the nucleic acid molecule of any one of claims 1, 2, 3, 4, or 5 under stringent conditions.
 7. An isolated nucleic acid molecule comprising a nucleotide sequence which is complementary to the nucleotide sequence of the nucleic acid molecule of any one of claims 1, 2, 3, 4, or
 5. 8. An isolated nucleic acid molecule comprising the nucleic acid molecule of any one of claims 1, 2, 3, 4, or 5, and a nucleotide sequence encoding a heterologous polypeptide.
 9. A vector comprising the nucleic acid molecule of any one of claims 1, 2, 3, 4, or
 5. 10. The vector of claim 9, which is an expression vector.
 11. A host cell transfected with the expression vector of claim
 10. 12. A method of producing a polypeptide comprising culturing the host cell of claim 11 in an appropriate culture medium to, thereby, produce the polypeptide.
 13. An isolated polypeptide selected from the group consisting of: a) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, wherein the fragment comprises at least 10 contiguous amino acids of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26; b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a complement of a nucleic acid molecule consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27 under stringent conditions; c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27; and d) a polypeptide comprising an amino acid sequence which is at least 60% identical to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26.
 14. The isolated polypeptide of claim 13 comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:1, SEQ ID NO:14, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, or SEQ ID NO:26.
 15. The polypeptide of claim 13, further comprising heterologous amino acid sequences.
 16. An antibody which selectively binds to a polypeptide of claim
 13. 17. A method for detecting the presence of a polypeptide of claim 13 in a sample comprising: a) contacting the sample with a compound which selectively binds to the polypeptide; and b) determining whether the compound binds to the polypeptide in the sample to thereby detect the presence of a polypeptide of claim 13 in the sample.
 18. The method of claim 17, wherein the compound which binds to the polypeptide is an antibody.
 19. A kit comprising a compound which selectively binds to a polypeptide of claim 13 and instructions for use.
 20. A method for detecting the presence of a nucleic acid molecule of any one of claims 1, 2, 3, 4, or 5 in a sample comprising: a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to a complement of the nucleic acid molecule; and b) determining whether the nucleic acid probe or primer binds to the complement of the nucleic acid molecule in the sample to thereby detect the presence of the nucleic acid molecule of any one of claims 1, 2, 3, 4, or 5 in the sample.
 21. The method of claim 20, wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.
 22. A kit comprising a compound which selectively hybridizes to a complement of the nucleic acid molecule of any one of claims 1, 2, 3, 4, or 5 and instructions for use.
 23. A method for identifying a compound which binds to a polypeptide of claim 13 comprising: a) contacting the polypeptide, or a cell expressing the polypeptide with a test compound; and b) determining whether the polypeptide binds to the test compound.
 24. The method of claim 23, wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of: a) detection of binding by direct detection of test compound/polypeptide binding; b) detection of binding using a competition binding assay; and c) detection of binding using an assay for 8099, 46455, 54414, 53763, 67076, 67102, 44181, 67084FL, or 67084alt activity.
 25. A method for modulating the activity of a polypeptide of claim 13 comprising contacting the polypeptide or a cell expressing the polypeptide with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.
 26. A method for identifying a compound which modulates the activity of a polypeptide of claim 13 comprising: a) contacting a polypeptide of claim 13 with a test compound; and b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide. 